Understanding Kidney Disease in African Americans

What You Will Learn

• African Americans account for about 30% of dialysis patients, highlighting severe health disparities.
• Risk factors for chronic kidney disease (CKD) include high rates of diabetes and hypertension, affecting over 50% of affected individuals.
• Genetic predispositions, particularly related to the APOL1 gene, significantly increase the risk of kidney disease in African American populations.
• Socioeconomic barriers, including limited healthcare access, contribute to delayed diagnosis and treatment of CKD in these communities.
• Early screening and regular health check-ups are crucial for prevention and management of kidney disease.
• Innovative dietary strategies, like plant-based diets, can positively impact kidney health and overall well-being.
• Community resources, such as free health screenings and education programs, are essential for raising awareness and supporting prevention efforts.

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INTRODUCTION

All patients with kidney disease (whether acute or chronic) should undergo an assessment of kidney function by estimating the glomerular filtration rate (GFR) from the serum creatinine. This measurement is used clinically to evaluate the degree of kidney impairment, to follow the course of the disease, and to assess the response to therapy. An attempt must also be made to obtain a specific diagnosis. The first step is a careful urinalysis, looking for albuminuria, hematuria, and cellular casts. Further evaluation may include quantification of albuminuria, kidney ultrasound, referral to a nephrologist, and a kidney biopsy. Nephrology referral is especially indicated when there is a rapid decline in kidney function, an elevated albumin-to-creatinine ratio (>300 mg/g), or urinary red blood cell casts. (See "Assessment of kidney function" and "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Urinalysis in the diagnosis of kidney disease".)

An overview of the general issues involved in the management of the patient with chronic kidney disease (CKD), including modalities to slow the rate of progression, will be presented here. The specific therapy of patients with particular kidney diseases is discussed separately in the appropriate topic reviews.

NATURAL HISTORY OF KIDNEY DISEASE

The initial injury to the kidney may result in a variety of clinical manifestations, ranging from asymptomatic hematuria to kidney failure requiring dialysis. Many individuals fully recover and subsequently suffer from little or no sequelae. Poststreptococcal glomerulonephritis in children, for example, most frequently has a long-term benign prognosis. By comparison, some patients, such as those with lupus nephritis, experience repeated and chronic insults to the kidney, thereby resulting in lasting damage. Furthermore, others in whom the initial disease is either inactive or cured may still develop progressive kidney disease due to hemodynamic and other mechanisms.

In addition to variations in the activity of the individual diseases, these different manifestations are partly due to how the kidney responds to injury. The kidney adapts to damage by increasing the filtration rate in the undamaged nephrons, a process called adaptive hyperfiltration. As a result, the patient with mild kidney insufficiency often has a normal or near-normal serum creatinine concentration. Additional homeostatic mechanisms (most frequently occurring within the renal tubules) permit the serum concentrations of sodium, potassium, calcium, and phosphorous and the total body water to also remain within the normal range, particularly among those with mild to moderate kidney disease. (See "Assessment of kidney function".)

Adaptive hyperfiltration, although initially beneficial, eventually causes damage to the glomeruli of the remaining nephrons, which is manifest by albuminuria and progressive kidney failure. This process appears to be responsible for the development of kidney failure among those in whom the original illness is either inactive or cured [1]. Estimates of single nephron glomerular filtration rate (SNGFR) in humans support hyperfiltration as a relevant pathophysiologic mechanism [2]. An elevated SNGFR was associated with risk factors for progression, including obesity, a family history of end-stage kidney disease (ESKD), and a greater degree of glomerulosclerosis and arteriosclerosis, suggesting compensation in remaining nephrons to maintain total GFR. The institution of measures to help prevent this process, such as treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, may slow progressive disease and even preserve kidney function [3]. Benefit is more likely if treatment is initiated before much irreversible scarring has occurred. (See "Secondary factors and progression of chronic kidney disease".)

The gradual decline in function in patients with CKD is initially asymptomatic. However, different signs and symptoms may be observed with advanced kidney failure, including volume overload, hyperkalemia, metabolic acidosis, hypertension, anemia, and mineral and bone disorders (MBDs). The onset of ESKD results in a constellation of signs and symptoms referred to as uremia.

Manifestations of uremia include anorexia, nausea, vomiting, pericarditis, peripheral neuropathy, and central nervous system abnormalities (ranging from loss of concentration and lethargy to seizures, coma, and death). No direct correlation exists between the absolute serum levels of blood urea nitrogen (BUN), creatinine, or GFR and the development of these symptoms. Some patients have relatively low levels of BUN (eg, 60 mg/dL [21.4 mmol/L] in an older patient) but are markedly symptomatic, while others have marked elevations (eg, 140 mg/dL [50 mmol/L]) but remain asymptomatic. To continue life, uremic patients require kidney replacement therapy with hemodialysis, peritoneal dialysis, or kidney transplantation. (See "Uremic toxins".)

Not all individuals have progressive loss of kidney function. Some studies show a high rate of progression, while others report relatively stable disease [4-6]. The rate of progression of CKD from one major stage to another varies based upon the underlying disease, presence or absence of comorbid conditions, treatments, socioeconomic status, individual genetics, ethnicity, and other factors. Episodes of acute kidney injury (AKI) may cause more rapid progression to ESKD in individual patients. (See "Kidney and patient outcomes after acute kidney injury in adults".)

Using epidemiologic data, general estimates for the rate of transition from an estimated GFR (eGFR) between 15 to 60 mL/min/1.73 m2 to end-stage disease may be approximately 1.5 percent per year, while the rate of transition from an eGFR >60 to <60 mL/min/1.73 m2 is approximately 0.5 percent per year [7,8].

The combination of low eGFR plus dipstick-positive albuminuria is associated with a significantly increased risk of progressive kidney disease, compared with either abnormality alone. This was shown in a retrospective study of the association between these measures and the 25-year incidence of ESKD of middle-aged males originally studied in the Multiple Risk Factor Intervention Study (MRFIT) [9]. The presence of 1+ dipstick albuminuria, 2+ dipstick albuminuria, eGFR <60 mL/min/1.73 m2, and a low eGFR plus 2+ albuminuria was associated with hazard ratios of 3.1, 15.7, 2.4, and 41, respectively, for the development of ESKD over a 25-year period.

DEFINITION AND CLASSIFICATION

CKD is defined as the presence of kidney damage (usually detected as urinary albumin excretion of ≥30 mg/day or equivalent) or decreased kidney function (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) for three or more months, irrespective of the cause. The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease (AKI).

Chronic kidney disease classification based upon glomerular filtration rate and albuminuria
Table 1
Classification, or staging, of CKD helps to guide management, including stratification of risk for progression and complications of CKD. Risk stratification is used to inform appropriate treatments and the intensity of monitoring and patient education. We agree with the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines that state that, among patients who are diagnosed using the criteria described above, staging of CKD should be done according to the following (table 1) [10] (see "Definition and staging of chronic kidney disease in adults"):

●Cause of disease

●Six categories of eGFR (G stages)

●Three categories of albuminuria (A stages)

Staging patients with CKD according to cause, eGFR, and albuminuria enhances risk stratification for the major complications of CKD (figure 1 and figure 2). As seen in these figures, more severely increased albuminuria is associated with a higher risk of adverse events at every level of eGFR.

A more detailed discussion of the definition and classification of CKD is provided separately. (See "Definition and staging of chronic kidney disease in adults".)

ASSOCIATION WITH CARDIOVASCULAR DISEASE, END-STAGE KIDNEY DISEASE, AND MORTALITY

There is a large body of evidence that patients with CKD have a substantial increase in cardiovascular risk that can be in part explained by an increase in traditional risk factors such as hypertension, diabetes, and the metabolic syndrome. CKD is also an independent risk factor for cardiovascular disease. Among patients with CKD, the risk of death, particularly due to cardiovascular disease, is much higher than the risk of eventually requiring dialysis. (See "Chronic kidney disease and coronary heart disease".)

The prevention and management of cardiovascular disease are critical for patients with CKD [11]. As an example, the increased intake of calcium (which is commonly given to treat hyperphosphatemia and may result in a high calcium-phosphorus product) may enhance coronary arterial calcification. Although controversial, this may be associated with the development of coronary atherosclerosis and is related to the presence and/or consequences of elevated serum phosphorus, calcium, and parathyroid hormone (PTH) levels. (See 'Mineral and bone disorders (MBD)' below and "Vascular calcification in chronic kidney disease".)

These and other observations have suggested that CKD should be considered a coronary equivalent and that aggressive risk factor reduction should be part of standard therapy of patients with CKD. (See "Chronic kidney disease and coronary heart disease", section on 'CKD as a CHD risk equivalent' and "Chronic kidney disease and coronary heart disease", section on 'Reduction of CHD risk in patients with CKD'.)

Patients with CKD are also at increased risk for the development of end-stage kidney disease (ESKD) as well as all-cause mortality. The competing risks of cardiovascular and ESKD vary depending on the population of patients studied and factors such as age, albuminuria, and type of kidney disease. (See "Chronic kidney disease and coronary heart disease", section on 'Competing risks of cardiovascular and end-stage kidney disease'.)

GENERAL MANAGEMENT OF CHRONIC KIDNEY DISEASE

The general management of the patient with CKD involves the following issues [12]:

●Treatment of reversible causes of kidney failure

●Preventing or slowing the progression of kidney disease

●Treatment of the complications of kidney failure

●Adjusting drug doses when appropriate for the level of estimated glomerular filtration rate (eGFR)

●Identification and adequate preparation of the patient in whom kidney replacement therapy will be required

Blood pressure control — Overall, the best evidence supports the following points (see "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Effect of goal blood pressure on progression of CKD'):

●More intensive versus less intensive blood pressure lowering reduces the risk of end-stage kidney disease (ESKD) in patients with albuminuric chronic kidney disease (CKD), but not in patients with nonalbuminuric CKD.

●However, more intensive blood pressure lowering may reduce mortality in patients with CKD (whether they have albuminuria or not), even though there is no benefit on kidney endpoints among patients without albuminuria. The mortality benefit from aggressive blood pressure lowering is most evident when patients are followed over the long term (ie, during posttrial follow-up), although an early reduction in mortality was noted in the Systolic Pressure Intervention Trial (SPRINT).

Hypertension is present in approximately 80 to 85 percent of patients with CKD [13]. Treating hypertension can slow the progression of albuminuric CKD and reduce the rate of cardiovascular complications. (See "Chronic kidney disease and coronary heart disease" and "Overview of hypertension in acute and chronic kidney disease".)

The choice of antihypertensive therapy in patients with nondiabetic and diabetic CKD is discussed separately. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of hypertension in patients with diabetes mellitus".)

Patients with CKD are frequently hypervolemic and require diuretic therapy to attain goal blood pressure. In patients with advanced CKD and refractory edema, both loop diuretics and thiazide diuretics may be needed. (See "Thiazides versus loop diuretics in the treatment of hypertension", section on 'Patients with chronic kidney disease' and "Overview of hypertension in acute and chronic kidney disease" and "Causes and treatment of refractory edema in adults".)

Goal blood pressure according to baseline risk for cardiovascular disease
Table 2
The optimal blood pressure in hypertensive patients with CKD and its impact on the progression of CKD is presented at length elsewhere (table 2). (See "Hypertension in adults: Goal blood pressure", section on 'Chronic kidney disease'.)

Slowing the rate of progression — Studies in experimental animals and humans suggest that progression in CKD may be due at least in part to secondary factors that are unrelated to the activity of the initial disease. The major factors are thought to be intraglomerular hypertension and glomerular hypertrophy (which are primarily responsible for the adaptive hyperfiltration described above), leading to glomerular scarring (glomerulosclerosis). Additional causes may include systemic hypertension, hyperlipidemia, metabolic acidosis, and tubulointerstitial disease. (See "Secondary factors and progression of chronic kidney disease".)

The major histologic manifestation of hemodynamically mediated kidney injury is secondary focal segmental glomerulosclerosis [14]. Thus, albuminuria typically is present in patients with progressive CKD, even in primary tubulointerstitial diseases such as reflux nephropathy.

Treating the underlying cause — Treatment of the underlying cause of CKD may halt or reduce the rate of its progression. The diagnostic evaluation of a patient with CKD to identify the cause is presented in detail separately. (See "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults".)

Details of treatment of the underlying cause of CKD (by cause) are detailed elsewhere. As examples:

●Autosomal dominant polycystic kidney disease (see "Autosomal dominant polycystic kidney disease (ADPKD): Treatment")

●Diabetic kidney disease (see "Treatment of diabetic kidney disease")

●Obesity (see "Overweight and obesity in adults: Health consequences", section on 'Chronic kidney disease' and "Obesity in adults: Overview of management")

●Glomerular disease (see "IgA nephropathy: Treatment and prognosis" and "Membranoproliferative glomerulonephritis: Treatment and prognosis" and "Anti-GBM (Goodpasture) disease: Treatment and prognosis" and "Membranous nephropathy: Treatment and prognosis")

●Viral infections (see "Kidney disease associated with hepatitis B virus infection", section on 'Treatment' and "Overview of kidney disease associated with hepatitis C virus infection", section on 'Treatment' and "HIV-associated nephropathy (HIVAN)", section on 'Initial therapy')

●Hematological disorders (see "Renal amyloidosis" and "Kidney disease in multiple myeloma and other monoclonal gammopathies: Treatment and prognosis", section on 'Patients with chronic kidney disease')

●Cardiac or hepatic disorders (see "Cardiorenal syndrome: Prognosis and treatment", section on 'Management' and "Hepatorenal syndrome: Treatment and prognosis")

Additional therapies — Patients with increased albuminuria, defined as measured or estimated albuminuria ≥30 mg/day (ACR ≥30 mg/g), should generally be prescribed specific agents to slow progression of CKD.

Patients with albuminuria — Therapy to slow the rate of progression in albuminuric patients with CKD, independent of treatment of the underlying disease, is centered on treating with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and attaining the blood pressure goal. In addition, such patients benefit from treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors.

●ACE inhibitors or ARBs – Patients with albuminuric CKD should attain specific goals related to a reduction in urinary albumin excretion to slow the rate of progression. Albuminuria goals and the use of ACE inhibitors or ARBs in such patients are discussed elsewhere. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of hypertension in patients with diabetes mellitus".)

In contrast to their renoprotective effects in albuminuric CKD, ACE inhibitors and ARBs do not appear to be more beneficial than other antihypertensive agents in patients with nonalbuminuric CKD. Recommendations for antihypertensive treatment in patients with nonalbuminuric CKD are discussed elsewhere. (See "Overview of hypertension in acute and chronic kidney disease".)

When used in patients with CKD, common side effects of angiotensin inhibition include a mild to moderate reduction in GFR and hyperkalemia. The decline in GFR occurs soon after the initiation of therapy or after an increase in dose. Hyperkalemia can occur soon after the initiation of therapy or later, if CKD is progressive. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)

●SGLT2 inhibitors – In patients with CKD and severely increased albuminuria (ie, measured albuminuria ≥300 mg/day or estimated by an albumin-creatinine ratio [ACR] ≥300 mg/g), we recommend treatment with an SGLT2 inhibitor, regardless of whether or not the patient has diabetes. This recommendation is broadly consistent with the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guideline [10]. We also suggest SGLT2 inhibitors in patients with CKD and moderately increased albuminuria (ie, measured albuminuria 30 to 299 mg/day or estimated by an ACR 30 to 299 mg/g), regardless of whether or not the patient has diabetes.

Patients who have CKD and severely increased albuminuria (with or without diabetes) benefit from treatment with SGLT2 inhibitors. The majority of studies demonstrating kidney protective benefits from these agents have been performed in patients with diabetic kidney disease. However, several large trials indicate that SGLT2 inhibitors are beneficial in albuminuric patients with nondiabetic kidney disease [15-18].

SGLT2 inhibitors act by blocking reabsorption of glucose in the proximal tubule through SGLT2, which lowers the renal glucose threshold and leads to substantial glycosuria. SGLT2 inhibitors have additional effects on the kidney that are likely independent of glycemic control. By blocking the cotransporter, they reduce sodium reabsorption. The resulting natriuresis reduces intravascular volume and blood pressure, but it also increases the delivery of sodium to the macula densa. Increased sodium delivery to the macula densa normalizes tubuloglomerular feedback and thereby reduces intraglomerular pressure (ie, reduces glomerular hyperfiltration) through constriction of the abnormally dilated afferent arteriole [17]. This and other mechanisms may explain the benefits of SGLT2 inhibitors on kidney disease progression [18]. (See "Diabetic kidney disease: Pathogenesis and epidemiology", section on 'Glomerular hyperfiltration'.)

The data supporting use of SGLT2 inhibitors among nondiabetic patients come from the following trials:

•In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial [15], 4304 individuals with eGFR 25 to 75 mL/min/1.73 m2 and urinary albumin to creatinine ratio of 200 to 5000 mg/g were randomly assigned to dapagliflozin (10 mg daily) or placebo. Approximately two-thirds of the participants had diabetes, and the cause of CKD in most of the remainder was either chronic glomerulonephritis or hypertensive nephrosclerosis [19]. At a median follow-up of 2.4 years, dapagliflozin reduced all-cause mortality (4.7 versus 6.8 percent), the incidence of ESKD (5.1 versus 7.5 percent), and the risk of 50 percent or greater decline in eGFR (5.2 versus 9.3 percent). The beneficial effect of dapagliflozin was similar in patients with and without diabetes and also in patients with and without severe CKD (ie, eGFR <30 mL/min/1.73 m2) [20].

•In the Study of Heart and Kidney Protection with Empagliflozin (EMPA-KIDNEY) trial, 6609 patients with eGFR 20 to 44 mL/min/1.73 m2 (regardless of albuminuria) or 45 to 89 mL/min/1.73 m2 (if albumin-to-creatinine ratio was at least 200 mg/g) were randomly assigned to empagliflozin 10 mg daily or placebo [16]. Less than half of participants had diabetes, and approximately half had urine ACR <300 mg/g. At two years, empagliflozin reduced the incidence of ESKD (3.3 versus 4.8 percent), the incidence of a sustained decline in eGFR to <10 mL/min/1.73 m2 (3.5 versus 5.1 percent), and the incidence of a sustained decrease in eGFR of 40 percent or more (10.9 versus 14.3 percent) [21]. The risks of all-cause mortality (4.5 versus 5.1 percent) and nonfatal cardiovascular events (4.3 versus 4.6 percent) were similar between the groups.

After two years of randomized therapy, participants in both treatment groups were entered into an open-label posttrial follow-up for an additional two years, during which time SGLT2 inhibitors could be prescribed at the discretion of the patients' clinicians [22]. The original trial assignments were used for the posttrial follow-up, with open-label SGLT2 inhibitors prescribed in 43 percent of the SGLT2 group and 40 percent of the placebo group. The benefits of empagliflozin observed during the full four years of follow-up were similar to the benefits noted during the initial two-year randomization period. Effects were similar in patients with and without diabetes, with various levels of baseline albuminuria, and regardless of the eGFR at the start of the study.

In a meta-analysis of these two trials, SGLT2 inhibitors reduced the risk of kidney failure (defined as the need for maintenance dialysis, kidney transplantation, or a sustained decline in eGFR to <10 to 15 mL/min/1.73 m2) compared with placebo (4.6 versus 6.3 percent; hazard ratio 0.72, 95% CI 0.56-0.91) [23].

Other

●Protein restriction − Protein restriction may slow the progression of CKD, although the optimal level and type of protein intake have not been determined. This issue is discussed elsewhere. (See "Dietary recommendations for patients with nondialysis chronic kidney disease".)

●Smoking cessation − Stopping smoking is associated with a slower rate of progression of CKD [24]. In an increasing number of studies, smoking also appears to correlate with an enhanced risk of developing kidney disease (primarily nephrosclerosis) as well as increasing the rate of progression among those with existing CKD [25].

●Treatment of chronic metabolic acidosis with supplemental bicarbonate may slow the rate of kidney function loss. (See "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease", section on 'Slowing of CKD progression'.)

●Glycemic control – Control of blood glucose can slow the development of albuminuria, the progression of moderately increased albuminuria to severely increased albuminuria, and GFR loss in diabetic patients. Treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may reduce the risk of kidney disease progression in patients with type 2 diabetes [3]. (See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Kidney outcomes' and "Treatment of diabetic kidney disease".)

Acute on chronic kidney disease — In addition to exacerbation of their original kidney disease, patients with CKD with a recent decrease in eGFR may be suffering from an underlying reversible process, which, if identified and corrected, may result in the recovery of function. This is sometimes termed "acute on chronic kidney disease."

Decreased kidney perfusion — Hypovolemia (such as vomiting, diarrhea, diuretic use, bleeding), hypotension (due to myocardial dysfunction or pericardial disease), infection (such as sepsis), and the administration of drugs that lower the eGFR (such as nonsteroidal antiinflammatory drugs [NSAIDs] and ACE inhibitors or ARBs) are common causes of potentially reversible declines in kidney function. In patients with CKD, hypovolemia should be diagnosed by history and physical examination rather than the urine sodium or fractional excretion of sodium. The kidney's normal response to hypoperfusion is to substantially lower the urine sodium concentration (<25 mEq/L) and the fractional excretion of sodium (<1 percent in patients with advanced kidney failure). However, the superimposition of a prerenal process among patients with CKD may not result in the expected low values, since the tubules in the diseased kidney are unable to reabsorb sodium so efficiently. If hypovolemia is suspected, a judicious trial of fluid repletion may result in the return of kidney function to the previous baseline. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury".)

Administration of nephrotoxic drugs — The administration of drugs or diagnostic agents is a frequent cause of worsening kidney function. Among patients with CKD, common offenders include aminoglycoside antibiotics (particularly with unadjusted doses), NSAIDs, and radiographic contrast material. The administration of such drugs should therefore be avoided or used with caution in patients with underlying CKD. (See "Manifestations of and risk factors for aminoglycoside nephrotoxicity" and "NSAIDs: Acute kidney injury" and "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management".)

Certain drugs also interfere with either creatinine secretion or the assay used to measure the serum creatinine. These include cimetidine, trimethoprim, cefoxitin, and flucytosine. In these settings, there will be no change in the true GFR; the clinical clue that this may have occurred is the absence of a concurrent elevation in the blood urea nitrogen (BUN). (See "Drugs that elevate the serum creatinine concentration".)

Urinary tract obstruction — Urinary tract obstruction should always be considered in the patient with unexplained worsening kidney function, although, in the absence of prostatic disease, it is much less common than decreased kidney perfusion. Patients with slowly developing obstruction typically have no changes in the urinalysis, no symptoms referable to the kidney, and initially maintain their urine output. Kidney ultrasonography is often performed to exclude urinary tract obstruction in patients with an unexplained elevation in the serum creatinine. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)

Treatment of the complications of severe CKD — A wide range of disorders may develop as a consequence of the loss of kidney function. These include disorders of fluid and electrolyte balance, such as volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction, such as anorexia, nausea, vomiting, fatigue, hypertension, anemia, malnutrition, hyperlipidemia, and bone disease.

One recommended diet, including suggestions for protein, fat, mineral, and water, is presented (table 3). This should be modified based upon the needs of the individual patient.

Volume overload — Sodium and intravascular volume balance are usually maintained until the eGFR falls below 10 to 15 mL/min/1.73 m2. However, the patient with mild to moderate CKD, despite being in relative volume balance, is less able to respond to rapid intake of sodium and is therefore prone to fluid overload.

Patients with CKD and volume overload generally respond to the combination of dietary sodium restriction and diuretic therapy, usually with a loop diuretic given daily. Some investigators have claimed that limiting sodium intake may also help decrease progression of CKD by lowering intraglomerular pressure [26]. We agree with the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines that sodium intake should be restricted to <2 g/day in adults with CKD, unless contraindicated [10]. (See "Loop diuretics: Dosing and major side effects" and "Causes and treatment of refractory edema in adults".)

Hyperkalemia — The ability to maintain potassium excretion at near-normal levels is generally maintained in patients with kidney disease as long as both aldosterone secretion and distal flow are maintained [27,28]. Thus, hyperkalemia generally develops in the patient who is oliguric or who has an additional problem such as a high-potassium diet, increased tissue breakdown, or hypoaldosteronism (due in some cases to the administration of an ACE inhibitor or ARB) [29]. Impaired cell uptake of potassium also may contribute to the development of hyperkalemia in advanced CKD. (See "Causes and evaluation of hyperkalemia in adults".)

Hyperkalemia due to ACE inhibitor or ARB therapy is most likely to occur in patients in whom the serum potassium concentration is elevated or in the high-normal range prior to therapy. This is discussed in detail separately. (See "Treatment and prevention of hyperkalemia in adults".)

There are several measures that may help prevent hyperkalemia in patients with CKD. These include ingestion of a low-potassium diet (eg, <40 to 70 mEq/day [1500 to 2700 mg/day]) and avoiding, if possible, the use of drugs that raise the serum potassium concentration, such as NSAIDs [30]. Nonselective beta blockers may result in a postprandial rise in the serum potassium concentration but do not cause persistent hyperkalemia. (See "Causes and evaluation of hyperkalemia in adults", section on 'Beta blockers' and "Patient education: Low-potassium diet (Beyond the Basics)".)

Metabolic acidosis — CKD can lead to a progressive metabolic acidosis [31-33], with the serum bicarbonate concentration tending to stabilize between 12 and 20 mEq/L and rarely falling below 10 mEq/L [32,34]. Metabolic acidosis may be treated with bicarbonate supplementation, which requires careful monitoring of volume status because bicarbonate is administered with sodium. (See "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease", section on 'Treatment of metabolic acidosis in CKD'.)

Mineral and bone disorders (MBD) — Hyperphosphatemia is a common complication of CKD. A tendency toward phosphate retention begins early in kidney disease due to the reduction in the filtered phosphate load. Although this problem is initially mild, with hyperphosphatemia being a relatively late event, phosphate retention is intimately related to the common development of secondary hyperparathyroidism. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

From the viewpoint of calcium and phosphate balance, the hypersecretion of parathyroid hormone (PTH) is initially appropriate since PTH can correct both hyperphosphatemia and hypocalcemia. As a result, phosphate balance and a normal serum phosphate concentration are generally maintained in patients with an eGFR of >30 mL/min/1.73 m2 [35]. The price paid is secondary hyperparathyroidism and the development of renal osteodystrophy. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Dietary phosphate restriction and oral phosphate binders may limit the development of secondary hyperparathyroidism in patients with CKD (table 4A-B). (See "Management of hyperphosphatemia in adults with chronic kidney disease".)

The increased intake of calcium may enhance coronary arterial calcification in this setting. This may predispose patients to coronary atherosclerosis and the presence and/or consequences of elevated serum phosphorus, calcium, and PTH levels (see "Vascular calcification in chronic kidney disease"). Relevant guidelines for managing MBD in CKD, as well as other KDIGO guidelines, can be accessed through the KDIGO website.

Changes in bone structure are an almost universal finding with progressive CKD [36]. The principal types of renal bone disease include osteitis fibrosa, osteomalacia, and adynamic bone disease. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Osteitis fibrosa results from secondary hyperparathyroidism. Although an exact relationship is unclear, PTH levels appear to increase when kidney function decreases beyond a certain threshold value, with evidence suggesting that hormone levels begin to rise when the creatinine clearance is <40 to 70 mL/min [37,38].

PTH levels should therefore be assessed among such patients as hormonal abnormalities are one of the earliest markers of abnormal mineral and bone metabolism with progressive CKD. Prevention and/or treatment of osteitis fibrosis in patients with predialysis CKD include dietary phosphate restriction, the administration of oral phosphate binders, and the administration of calcitriol (or vitamin D analogs) to suppress the secretion of PTH.

Circulating calcitriol (1,25-dihydroxyvitamin D), the most active metabolite of vitamin D, is principally synthesized in the kidney. Circulating calcitriol levels begin to fall when the eGFR is <40 mL/min/1.73 m2 and are typically markedly reduced in patients with ESKD. In addition to the loss of functioning kidney mass, calcitriol production is also reduced by phosphate retention. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Calcimimetics are agents that allosterically increase the sensitivity of the calcium-sensing receptor in the parathyroid gland to calcium. The calcium-sensing receptor is the principal factor regulating parathyroid gland PTH secretion and hyperplasia. The separate target offers the potential to suppress PTH secretion by mechanisms complementary and potentially synergistic with vitamin D analogs that target the vitamin D receptor. Although not approved for patients with CKD not yet on dialysis, cinacalcet is an emerging option in the treatment of secondary hyperparathyroidism in patients with CKD who do not require dialysis.

Target serum levels for PTH, as well as the approach to the management of this issue, are discussed separately. (See "Management of secondary hyperparathyroidism in adult patients with nondialysis chronic kidney disease".)

Hypertension — Hypertension is present in approximately 80 to 85 percent of patients with CKD [13]. It can be a cause or consequence of CKD. (See 'Blood pressure control' above.)

Anemia — The anemia of CKD is typically normocytic and normochromic and is due primarily to reduced production of erythropoietin by the kidney (a presumed reflection of the reduction in functioning kidney mass) and to shortened red cell survival [39]. Anemia is a common feature in many patients with nondialysis-dependent CKD, with anemia becoming increasingly common as eGFRs decline below 30 mL/min/1.73 m2 [40,41], particularly among diabetics [42]. As an example, based upon over 15,000 participants in the National Health and Nutrition Examination Survey (NHANES), the prevalence of anemia (hemoglobin [Hb] <12 g/dL in males and <11 g/dL in females) increased from 1 percent at an eGFR of 60 mL/min/1.73 m2 to 9 percent at an eGFR of 30 mL/min/1.73 m2 and to 33 to 67 percent at an eGFR of 15 mL/min/1.73 m2 [40]. (See "Treatment of anemia in nondialysis chronic kidney disease".)

The 2024 KDIGO guideline suggests that, among patients who do not have anemia, the Hb concentration should be checked when it is clinically indicated and at least yearly among all patients with stage 3 CKD (ie, eGFR 30 to 59 mL/min/1.73 m2), at least every six months among patients with stage 4 to 5 CKD (ie, eGFR ≤29 mL/min/1.73 m2), and at least every three months among patients who are on dialysis [10]. Among patients with known anemia who are not treated with erythropoiesis-stimulating agents (ESAs), Hb should be checked when it is clinically indicated and at least every three months among patients with stage 3 to 5 (ie, eGFR ≤59 mL/min/1.73 m2) who are not on hemodialysis (including patients who are on peritoneal dialysis); patients on hemodialysis should be monitored monthly. (See "Definition and staging of chronic kidney disease in adults", section on 'Staging of CKD'.)

As stated in the KDIGO guideline, the evaluation of anemia in those with CKD should begin when the Hb level is <12 g/dL in females and <13 g/dL in adult males [43,44]. These values are consistent with the World Health Organization (WHO) definition of anemia [45]. If untreated, the Hb level of patients with advanced CKD normally stabilizes at approximately 8 g/dL in the absence of bleeding or hemolysis.

The anemia observed with CKD is largely diagnosed by excluding nonrenal causes of anemia in the patient with a suitably decreased eGFR. The evaluation of patients should therefore include red blood cell indices, absolute reticulocyte count, serum iron, total iron-binding capacity, percent transferrin saturation, serum ferritin, white blood cell count and differential, platelet count, B12 and folate concentrations if the mean corpuscular volume (MCV) is increased, and testing for blood in stool. This work-up should be performed prior to administering ESA therapy. (See "Diagnostic approach to anemia in adults".)

The evaluation and treatment of iron deficiency in patients with CKD are presented elsewhere. (See "Diagnosis of iron deficiency in chronic kidney disease" and "Treatment of iron deficiency in patients on dialysis" and "Treatment of iron deficiency in patients with nondialysis chronic kidney disease (CKD)".)

Although primarily used in patients with ESKD, ESAs such as erythropoietin and darbepoetin alfa also correct the anemia in those with CKD who do not require dialysis. (See "Treatment of anemia in nondialysis chronic kidney disease".)

The use of ESAs for the treatment of anemia in patients with CKD, including the KDIGO recommendations, is discussed in detail separately. (See "Treatment of anemia in patients on dialysis".)

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF PHIs) are an emerging therapy for the treatment of anemia in patients requiring dialysis and those with nondialysis-requiring CKD. (See "Treatment of anemia in patients on dialysis", section on 'HIF PHIs' and "Treatment of anemia in nondialysis chronic kidney disease", section on 'Uncertain role for hypoxia-inducible factor prolyl hydroxylase inhibitors'.)

Dyslipidemia — Abnormal lipid metabolism is common in patients with kidney disease [46]. The primary finding in CKD is hypertriglyceridemia, with the total cholesterol concentration usually being normal (perhaps due in part to malnutrition in some patients). All CKD patients should be evaluated and potentially treated for dyslipidemia. (See "Lipid management in patients with nondialysis chronic kidney disease", section on 'Treatment' and "Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis)", section on 'Lipid modification' and "Lipid abnormalities after kidney transplantation", section on 'Treatment'.)

Follow-up testing may be performed among patients who are age <50 years who are not already on a statin in order to assess cardiovascular risk and the need for statin therapy. Follow-up evaluation may also be performed to assess adherence to statin treatment, if there is a change in the modality of kidney replacement therapy, or if there is concern about new secondary causes of dyslipidemia (such as nephrotic syndrome, hypothyroidism, diabetes, excessive alcohol consumption, or liver disease).

The treatment of hypertriglyceridemia in CKD patients, including the KDIGO recommendations, is discussed elsewhere. (See "Lipid management in patients with nondialysis chronic kidney disease", section on 'Hypertriglyceridemia' and "Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis)", section on 'Hypertriglyceridemia' and "Lipid abnormalities after kidney transplantation", section on 'Treatment'.)

In the patient with hypercholesterolemia, a statin with or without ezetimibe can effectively and safely lower the plasma cholesterol concentration to or near acceptable levels. Given that CKD is associated with an adverse cardiovascular prognosis, CKD is considered a coronary heart disease equivalent [47]. (See "Chronic kidney disease and coronary heart disease".)

The goal low-density lipoprotein cholesterol (LDL-C) is discussed elsewhere. (See "Lipid management in patients with nondialysis chronic kidney disease", section on 'Treatment'.)

Although some studies suggested that lipid lowering with statins could reduce albuminuria and slow progression of kidney disease, subsequent large trials found no beneficial effect on kidney outcomes [48-52]; therefore, statin therapy is not useful solely for kidney protection.

Sexual dysfunction — Significant abnormalities in sexual and reproductive function are frequently observed in patients with advanced kidney disease. As an example, >50 percent of uremic males complain of symptoms that include erectile dysfunction, decreased libido, and marked declines in the frequency of intercourse [53]; in addition, disturbances in menstruation and fertility are commonly encountered in females with CKD, usually leading to amenorrhea by the time the patient reaches ESKD. (See "Epidemiology and etiologies of male sexual dysfunction".)

An important clinical implication of these abnormalities is that pregnancy that is carried to term is uncommon in females with a plasma creatinine concentration of ≥3 mg/dL (265 micromol/L) [54]. (See "Pregnancy and contraception in patients with nondialysis chronic kidney disease".)

Treatment of complications of end-stage kidney disease — Once the patient has reached the stage of near ESKD (eGFR <15 mL/min/1.73 m2), signs and symptoms related to uremia begin to occur, such as malnutrition, anorexia, nausea, vomiting, fatigue, sexual dysfunction, platelet dysfunction, pericarditis, and neuropathy.

Malnutrition — Malnutrition is common in patients with advanced CKD because of a lower food intake (principally due to anorexia), decreased intestinal absorption and digestion, and metabolic acidosis [55-57]. Among participants age ≥60 years in the United States Third NHANES, an eGFR <30 mL/min/1.73 m2 was independently associated with malnutrition (odds ratio [OR] 3.6) [56]. Many additional studies have shown a strong correlation between malnutrition and death in maintenance dialysis patients. (See "Indications for initiation of dialysis in chronic kidney disease".)

It is therefore desirable to monitor the nutritional status of patients with CKD. A low plasma concentration of albumin may be indicative of malnutrition. To best assess nutritional status, the serum albumin concentration and body weight should be measured serially; these should be measured approximately every one to three months for those with eGFRs <20 mL/min/1.73 m2 and more frequently, if necessary, for those with eGFRs ≤15 mL/min/1.73 m2 [58]. (See "Assessment of nutritional status in patients on hemodialysis".)

The desire to maintain adequate nutrition among patients with CKD clearly competes with attempts to slow the progression of kidney failure with the use of a low-protein diet. This issue is discussed elsewhere. (See "Dietary recommendations for patients with nondialysis chronic kidney disease".)

Overall, the diet of most patients with CKD should provide approximately 30 to 35 kcal/kg per day [59]. One recommended diet, including suggestions for protein, fat, mineral, and water, is presented in the table (table 3). The Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for nutrition in CKD, as well as other KDOQI guidelines, can be accessed through the National Kidney Foundation's website.

Uremic bleeding — An increased tendency to bleeding is present in patients with CKD. This appears to correlate most closely with prolongation of the bleeding time due primarily to impaired platelet function. (See "Uremic platelet dysfunction".)

No specific therapy is required in asymptomatic patients. However, correction of the platelet dysfunction is desirable in patients who are actively bleeding or who are about to undergo a surgical or invasive procedure (such as a kidney biopsy). A number of different modalities can be used in this setting, including the correction of anemia, the administration of desmopressin (DDAVP), cryoprecipitate, estrogen, and the initiation of dialysis. (See "Uremic platelet dysfunction".)

Pericarditis — Advances in management have decreased the incidence of pericarditis in patients with CKD, but this problem is still associated with significant morbidity and occasional mortality.

Fever, pleuritic chest pain, and a pericardial friction rub are the major presentations of uremic pericarditis. One relatively characteristic feature of uremic pericarditis is that the electrocardiogram does not usually show the typical diffuse ST and T wave elevation, presumably because this is a metabolic pericarditis, and epicardial injury is uncommon. Thus, the finding of these abnormalities suggests some other cause for the pericarditis. The occurrence of pericarditis in a patient with mild to moderate CKD is another clue that the kidney disease is probably not responsible.

The development of otherwise unexplained pericarditis in a patient with advanced kidney failure is an indication to institute dialysis (providing there is no circulatory compromise or evidence of impending tamponade) (see below). Most patients with uremic pericarditis respond rapidly to dialysis, with resolution of chest pain as well as a decrease in the size of the pericardial effusion.

Uremic neuropathy — Dysfunction of the central and peripheral nervous system including encephalopathy (impaired mental status progressing, if untreated, to seizures and coma), polyneuropathy, and mononeuropathy are important complications of ESKD. They have become much less common because of the tendency to earlier initiation of dialysis.

Sensory dysfunctions, characterized by the restless leg or burning feet syndromes, are frequent presentations of uremic neuropathy. These complications are usually absolute indications for the initiation of dialysis. The extent of recovery from uremic neuropathy is directly related to the degree and extent of dysfunction prior to the

Recap of Key Points

Here is a quick recap of the important points discussed in the article:

• African Americans are nearly four times more likely to experience kidney failure than their white counterparts.
• About 15% of African American adults are living with chronic kidney disease (CKD).
• Key risk factors for kidney disease include diabetes, hypertension, and genetic predispositions.
• Obesity and cardiovascular diseases significantly increase the risk of CKD.
• Socioeconomic barriers such as limited access to healthcare affect timely diagnosis and treatment.
• Early screening and education are vital for better health outcomes in kidney disease.
• Innovative treatments and culturally relevant health education can empower communities to combat kidney disease effectively.