Chronic Glomerulonephritis Treatment & Management

Updated: Feb 01, 2017
  • Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Treatment

Approach Considerations

Patients with chronic kidney disease (CKD) who are admitted to the hospital should receive careful monitoring of weight, intake, output, and renal function so that acute kidney injury (AKI) can be diagnosed and treated early if it occurs,. All potentially nephrotoxic agents must be adjusted for the degree of CKD. Furthermore, agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides, and intravenous (IV) contrast media must be avoided unless the benefits clearly outweigh the risks; they are strongly associated with AKI.

Progression from CKD to end-stage renal disease (ESRD) can be slowed by a variety of measures, including aggressive control of diabetes, hypertension, and proteinuria. Dietary protein restriction, phosphate restriction, and hyperlipidemia control may have significant impact on retarding disease progression. In obese patients, weight reduction and bariatric surgery may have beneficial effects on CKD. [13]

Specific therapies for some glomerular diseases (eg, lupus) should be implemented in appropriate settings. Aggressively manage anemia and renal osteodystrophy (eg, hyperphosphatemia, hypocalcemia, or hyperparathyroidism) before initiating renal replacement therapy. Also, aggressively manage comorbid conditions, such as heart disease and diabetes.

Nephrotic patients (urinary protein excretion >3.5 g/day) may have hyperlipidemia. As a part of cardiovascular health care, the lipid profile should be checked, and lipid-lowering therapy should be started for patients with hyperlipidemia.

Steroid therapy may induce or exacerbate diabetes, hypertension, weight gain, fat redistribution in the trunk (buffalo hump) and face (moon facies), cosmetic problems (eg, hirsutism and acne), and osteoporosis.

Monitor fasting blood glucose levels and blood pressure. Obtain baseline bone densitometry values. Repeat bone densitometry for bone pain. Oral calcium supplements (1 g/day) and vitamin D (400-800 IU/day) are recommended for prophylaxis against osteoporosis.

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Pharmacologic Therapy

Blood pressure management

The target blood pressure for patients with proteinuria in excess of 1 g/day is less than 125/75 mm Hg; for patients with proteinuria of less than 1 g/day, the target pressure is less than 130/80 mm Hg.

Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used and are usually the first choice for treatment of hypertension in patients with chronic kidney disease (CKD). ACEIs are renoprotective agents that have additional benefits beyond lowering pressure. They effectively reduce proteinuria, in part by reducing the efferent arteriolar vascular tone, thereby decreasing intraglomerular hypertension.

In particular, ACEIs have been shown to be superior to conventional therapy in slowing the decline of the glomerular filtration rate (GFR) in patients with diabetic and nondiabetic proteinuric nephropathies. Therefore, ACEIs should be considered for treatment of even normotensive patients with significant proteinuria. [14]

The role of angiotensin II receptor blockers (ARBs) in renal protection is increasingly being established, and these medications have been found to retard the progression of CKD in patients with diabetic or nondiabetic nephropathy, much as ACEIs do. [15]

A combination of ACEI therapy and ARB therapy has been shown to achieve better pressure control and preservation of renal function than either therapy alone could. Therefore, in patients without hyperkalemia or an acute rise in serum creatinine levels after the use of either therapy, combination therapy should be attempted. [16]

However, in patients with vascular disease or diabetes, combination ACEI and ARB therapy has been associated with increased adverse effects, including hyperkalemia, worsening renal function, and mortality. As such, combination ACEI and ARB therapy should not be used to treat hypertension in these groups of patients with CKD. [17]

Diuretics are often required because of decreased free-water clearance, and high doses may be required to control edema and hypertension when the GFR falls below 25 mL/min. Diuretics are also useful in counteracting the hyperkalemic potential of ACEIs and ARBs. However, they should be used with caution when given together with ACEIs or ARBs because the decline in intraglomerular pressure induced by ACEIs or ARBs may be exacerbated by the volume depletion induced by diuretics, potentially precipitating ARF.

Beta blockers, calcium channel blockers, [18] central alpha2 agonists (eg, clonidine), alpha1 antagonists, and direct vasodilators (eg, minoxidil and nitrates) may be used to achieve the target pressure.

Fibrosis inhibition

Because progressive fibrosis is the hallmark of chronic glomerulonephritis, some investigators have focused on finding inhibitors of fibrosis in an attempt to slow progression. Of the many compounds that have been considered, pirfenidone, an inhibitor of transforming growth factor beta and hence of collagen synthesis, has emerged as the best candidate.

Cho et al, in an open-label study involving 21 patients with idiopathic and postadaptive focal segmental glomerulosclerosis, found that pirfenidone yielded a median 25% improvement in the rate of decline of the estimated GFR; the drug did not affect proteinuria or blood pressure. [19] Among the adverse events attributed to therapy were dyspepsia, sedation, and photosensitive dermatitis. It is hoped that pirfenidone therapy will prove an effective means of slowing progressive fibrosis; however, more studies are needed.

Role of antioxidants (bardoxolone)

Cells have the ability to produce antioxidants, anti-inflammatory and detoxifying enzymes that are useful for cell viability, but this pathway is constantly being inhibited by an enzyme called KEAP. Inhibition of KEAP may therefore improve the antioxidant activity of cells and promote cell viability. Bardoxolone, an oleanolic acid derivative, blocks Keap and has been postulated as a potential mechanism to retard progression of CKD. In one study, patients receiving bardoxolone had significant increases in the mean (± standard deviation) estimated GFR, as compared with placebo, at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone may have promise for the treatment of CKD, however a phase 3 randomized clinical trial failed to achieve the primary end point and was associated with side effects and so the study was stopped. [20] It is not likely that Bardoxolone will be used for renoprotection any time soon.

Role of sodium bicarbonate

Sodium bicarbonate has been shown to reduce tubulointerstitial injury and endothelin production with substantial benefits in slowing progressive kidney damage. In one study on patients with advanced kidney failure, the administration of sodium bicarbonate preserved GFR decline. [20] Even in patients with relatively preserved GFR in stage 2 CKD, the administration of sodium bicarbonate was shown to preserve kidney function over 5 years. [21] A study in patients with stage 4 CKD found that 1 year of consuming a diet that included fruits and vegetables dosed to reduce dietary acid by half had effects comparable to those of daily oral sodium bicarbonate at 1.0 mEq/kg per day. [22]

Role of direct renin inhibitors

Preliminary studies using aliskiren, [23] a direct renin inhibitor, show reductions in proteinuria over 6 months, but larger studies did not show benefit.

Management of other problems

Renal osteodystrophy can be managed early by replacing vitamin D and by administering phosphate binders. Seek and treat nonuremic causes of anemia, such as iron deficiency, before instituting therapy with erythropoietin.

Treat hyperlipidemia (if present) to reduce overall cardiovascular comorbidity, even though evidence for lipid lowering in renal protection is lacking.

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Renal Replacement Therapy

Discuss options for renal replacement therapy (eg, hemodialysis, peritoneal dialysis, and renal transplantation).

Arrange permanent vascular access when the GFR falls below 20-25 mL/min, when the serum creatinine level exceeds 4 mg/dL, or when the rate of increase in the serum creatinine level indicates the need for dialysis within 1 year. Arteriovenous fistulas are preferred to arteriovenous grafts because of their long-term high-patency rates and should be placed whenever possible. Place peritoneal dialysis catheters 2-3 weeks before anticipated dialysis therapy.

Preemptive transplantation before the initiation of dialysis results in better survival than transplantation after the initiation of dialysis. Therefore, preemptive transplantation should be explored from live donors. Patients without live donors can be placed on the deceased donor wait list when the GFR falls below 20 mL/min to accrue time. Patients who opt for no treatment when it is indicated should be informed of imminent renal failure in a shorter time.

Expose patients to educational programs for early rehabilitation from dialysis or transplantation.

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Consultations

Patients with any evidence of kidney disease should be referred to a kidney specialist (ie, a nephrologist). Early referral of patients with CRF (serum creatinine, 1.5-2 mg/dL) to a nephrologist is important for managing complications and organizing the transition to renal replacement therapy. Some evidence indicates that early referral of CRF patients to a nephrologist improves the short-term outcome. The nephrologist will usually determine the frequency of visits on the basis of the degree of CKD.

When dialysis is imminent, a surgical consultation should be sought for creation of an arteriovenous fistula or graft to allow insertion of a peritoneal dialysis catheter. Consultation with a transplant surgeon is appropriate for evaluation for kidney transplantation.

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Diet and Activity

Protein-restricted diets (0.4-0.6 g/kg/day) are controversial but may be beneficial in slowing the decline in the GFR and reducing hyperphosphatemia (serum phosphate > 5.5 mg/dL) in patients with serum creatinine levels higher than 4 mg/dL. Monitor these patients for signs of malnutrition, which may contraindicate protein restriction. Educate patients about how potassium-rich diets help control hyperkalemia. Many dietary restrictions are no longer necessary with the initiation of renal replacement therapy.

Encourage patients to increase their activity level as tolerated. Increased activity may aid in blood pressure control.

In obese patients with mild to moderate CKD, weight loss may help reverse renal dysfunction, manifesting as reduction in proteinuria and albuminuria. [24, 13]

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