Chronic Kidney Disease Treatment & Management

Early diagnosis and treatment of the underlying cause and/or institution of secondary preventive measures is imperative in patients with chronic kidney disease. These may delay, or possibly halt, progression. Early nephrologic referral is of extreme importance.

The medical care of patients with chronic kidney disease should focus on the following:

• Delaying or halting the progression of chronic kidney disease
• Treating the pathologic manifestations of chronic kidney disease
• Timely planning for long-term renal replacement therapy

Patients with chronic kidney disease acutely presenting with indications for dialytic therapy should be transferred to a hospital center where acute dialysis can be performed.

The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) has issued 13 clinical practice guidelines for managing all stages of chronic kidney disease and related complications.

Treatment of the underlying condition if possible is indicated.

Aggressive blood pressure control to target values per current guidelines is indicated. Systolic blood pressure control is considered more important and is also considered difficult to control in elderly patients with chronic kidney disease.

Peralta et al conducted a diverse, community-based study that determined high SBP appeared to account for most of the risk of progression to ESRD. The risk began at an SBP of 140 mm Hg, as opposed to the current recommended goal of less than 130 mm Hg. The highest risk was found among patients with an SBP of at least 150 mm Hg. In order to improve BP control in chronic kidney disease, treatment approaches that lower SBP may be required.^[16]

Use angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) as tolerated, with close monitoring for renal deterioration and for hyperkalemia (see the image below). Avoid these agents in advanced renal failure, bilateral renal artery stenosis [RAS], or RAS in a solitary kidney.

Data support the use of ACE inhibitors or ARBs in diabetic kidney disease with or without proteinuria. However, in nondiabetic kidney disease, these agents are effective in retarding the progression of disease among patients with proteinuria of less of than 500 mg/d.

Aggressive glycemic control per the American Diabetes Association (ADA) recommendations (target HbA1C < 7%) is indicated.

Although the Modification of Diet in Renal Disease (MDRD) Study failed to show the effect of protein restriction in retardation of the progression of kidney disease, a meta-analysis suggests a beneficial role for protein restriction. The National Kidney Foundation guidelines suggest that if a patient is started on protein restriction, the physician needs to closely monitor the patient's nutritional status. Predialysis low serum albumin is associated with a poor outcome among dialysis patients.

A small trial (n=61) by Fishbane et al found that paricalcitol (Zemplar), a synthetic analog of calcitriol, can reduce protein excretion in patients with chronic kidney disease.^[17] In this double-blind, randomized study, which compared paricalcitol, 1 mg/d, with placebo for 6 months, more patients in the paricalcitol group achieved a 10% reduction in proteinuria than did members of the control group (57.1% vs 25.9%, respectively).

Treatment of hyperlipidemia to target levels per current guidelines is indicated.

Avoidance of nephrotoxins, including IV radiocontrast, nonsteroidal anti-inflammatory agents (NSAIDs), and aminoglycosides is indicated.

A study by Plantinga et al found that a great number of individuals with chronic kidney disease may be unaware of their disease and thus may be at risk for further kidney injury through use of NSAIDs. Those who knew of their chronic kidney disease were less likely to use NSAIDs, suggesting that primary care physicians should be involved in communication regarding the risks of NSAID.^[18]

Encourage smoking cessation, as smokers tend to reach end-stage renal disease (ESRD) earlier than nonsmokers. A large-population Norwegian study found that although smoking posed a great risk factor for the future onset of kidney failure, cessation decreased the risk, especially in men, who tended to be heavier smokers than women in this cross-section.^[19]

The following should be addressed:

• Treat anemia when hemoglobin level is below 10 g/dL with erythropoiesis stimulating agents (ESAs) such as epoetin alfa, darbepoetin alfa, or peginesatide
• Hyperphosphatemia with dietary phosphate binders and dietary phosphate restriction
• Hypocalcemia with calcium supplements with or without calcitriol
• Hyperparathyroidism with calcitriol or vitamin D analogs
• Volume overload with loop diuretics or ultrafiltration
• Metabolic acidosis with oral alkali supplementation
• Uremic manifestations with long-term renal replacement therapy (hemodialysis, peritoneal dialysis, or renal transplantation)
• Cardiovascular complications

A study by Wald et al found that patients with increased left ventricular mass who underwent in-center nocturnal hemodialysis (3 times/week, 7-8 h/session in the dialysis unit) experienced regression, forecasting a more positive cardiovascular outcome.^[20]

With erythropoietin treatment, the goal is a hemoglobin level of 11-12 g/dL, as normalization of hemoglobin in patients with chronic kidney disease stages 4-5 has been associated with an increased risk of combined outcome. Before starting erythropoietin, iron stores should be checked. The aim is to keep iron saturation at 30-50% and ferritin at 200-500.

A study by Shurraw et al showed that in people with non–hemodialysis-dependent CKD, a hemoglobin A(1c) level higher than 9% is connected with worse clinical outcomes. Lower levels of hemoglobin A(1c) also seemed to be associated with excess mortality. Appropriate and timely control of the hemoglobin A(1c) level in people with diabetes mellitus and CKD may be more important than previously realized, but findings also suggest that intensive glycemic control may lead to increased mortality.^[21]

London et al summarized the best evidence and the Kidney Disease Improving Global Outcomes (KDIGO) recommendations on how to manage chronic kidney disease–mineral and bone disorder.^[22] The KDIGO guidelines were issued after weighing the quality and the depth of evidence, when available, and propose a common-sense approach to the evaluation and treatment of mineral and bone disorder in different stages of chronic kidney disease.

The evidence for the benefits and risks of correcting metabolic acidosis is very limited, with no randomized controlled trials in patients not yet in end-stage renal disease (ESRD), none in children, and only 3 small trials in dialysis patients. These trials suggest that there may be some beneficial effects on both protein metabolism and bone metabolism, but the trials were underpowered to provide robust evidence. Experts recommend alkali therapy to maintain the serum bicarbonate concentration above 22 mEq/L.

De Brito-Ashurst et al found that patients with chronic kidney disease who receive bicarbonate supplementation show a slower decline in renal function.^[23] In this study, 134 adult patients with chronic kidney disease (ie, creatinine clearance [CrCl] 15-30 mL/min/1.73 m² and serum bicarbonate 16-20 mmol/L) were randomly assigned to receive oral sodium bicarbonate supplementation or standard care for 2 years. A slower decline in CrCl was observed in the bicarbonate group than in the control group (1.88 vs 5.93 mL/min/1.73 m²).

Patients in the bicarbonate group were also less likely to experience rapid disease progression than were members of the control group (9% vs 45%), and fewer patients who received bicarbonate supplementation developed ESRD (6.5% vs 33%). In addition to the benefits listed above, nutritional parameters improved with bicarbonate supplementation.

Indications for renal replacement therapy include the following:

• Severe metabolic acidosis
• Hyperkalemia
• Pericarditis
• Encephalopathy
• Intractable volume overload
• Failure to thrive and malnutrition
• Peripheral neuropathy
• Intractable gastrointestinal symptoms
• In asymptomatic patients, glomerular filtration rate (GFR) of 5-9 mL/min^[24]

Consider the following:

• Early education regarding natural disease progression, different dialytic modalities, renal transplantation, patient option to refuse or discontinue chronic dialysis
• Timely placement of permanent vascular access (arrange for surgical creation of primary arteriovenous fistula, if possible, and preferably at least 6 months in advance of anticipated date of dialysis)
• Timely elective peritoneal dialysis catheter insertion
• Timely referral for renal transplantation

Protein restriction early in chronic kidney disease as a means to delay a decline in the GFR is controversial; however, as the patient approaches chronic kidney disease stage 5, this strategy is recommended to delay the onset of uremic symptoms. Patients with chronic kidney disease who already are predisposed to becoming malnourished are at higher risk for malnutrition with overly aggressive protein restriction. Malnutrition is a well-established predictor of increased morbidity and mortality in the ESRD population and must be avoided if possible.

A meta-analysis found that dietary salt reduction significantly reduced blood pressure in individuals with type 1 or type 2 diabetes.^[25] Similar results were observed in hypertensive patients with chronic kidney disease with bedtime dosing of at least one antihypertensive medication.^[26] These findings, along with other evidence relating salt intake to blood pressure and albuminuria in hypertensive and normotensive patients, make a strong case for a reduction in salt intake as a means of slowing the progression of diabetic nephropathy. The recommendation for the general population in public health guidelines is less than 5-6 g/d. Dietary salt reduction may help slow progression of kidney disease in both type 1 and type 2 diabetes.

The following dietary restrictions may also be indicated:

• Phosphate restriction starting early in chronic kidney disease
• Potassium restriction
• Sodium and water restriction as needed to avoid volume overload

The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) has issued a Clinical Practice Guideline for Nutrition in Chronic Renal Failure, as well as a 2008 revision of recommendations for Nutrition in Children with Chronic Kidney Disease.

A randomized controlled trial by Slagman et al found that moderate dietary sodium reduction (approximately 2500 mg/day of Na+ or 6 g/d of NaCl) added to ACE inhibition compared with dual blockade (ACE inhibitor and angiotensin receptor blocker) was more effective in reducing both proteinuria and blood pressure in nondiabetic patients with modest chronic kidney disease. Furthermore, low-sodium diet added to dual therapy yielded additional reductions in both blood pressure and proteinuria, emphasizing the beneficial effect of dietary salt reduction in the management of nondiabetic patients . ^[27]

Vegter et al found that among patients with chronic kidney disease but without diabetes, a high dietary salt (>14 g daily) intake interfered with the antiproteinuric effect of ACE inhibitor therapy and increased the risk for ESRD.^[28]

A study by Goraya et al shows that simple dietary changes in subjects with chronic kidney disease, in favor of fruits and vegetables, may help reduce kidney injury. The study concluded that a reduction in dietary acid aided by fruits and vegetables may be an effective adjunct to ACE inhibition and blood pressure reduction in patients with hypertension and potentially other nephropathies.^[29]

Consultations may include the following:

• Early nephrology referral (decreases morbidity and mortality)
• Renal dietitian
• Vascular surgery for permanent vascular access
• General surgery for peritoneal catheter placement
• Referral to renal transplant center

Patients with chronic kidney disease should be referred to a nephrologist early in the course of their disease and have continued nephrologic follow-up until initiation of chronic renal replacement therapy.

A multidisciplinary approach to care, including involvement of the nephrologist, primary care physician, renal dietitian, nurse, and social worker, should be initiated early in the course of chronic kidney disease, with close patient follow-up.

Patients should be monitored for obstructive sleep apnea (OSA), which occurs with increased frequency in patients receiving dialysis. In addition, a Japanese study has shown a connection between OSA and nondialysis chronic kidney disease. Sakaguchi et al found a high incidence (65%) of OSA in patients with nondialysis chronic kidney disease, with about one third of those having moderate or severe OSA. The study also found that decreased GFR was associated with an increased risk of OSA.^[30]

A study by Navaneethan et al found a connection between low levels of 25-hydroxyvitamin D and all-cause mortality in patients with nondialysis chronic kidney disease.^[31]