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Renal Manifestations of HIV
  Source: http://hivinsite.ucsf.edu
HIV InSite Knowledge Base Chapter
December 2003
Rudolph A. Rodriguez, MD, University of California San Francisco

Acute Renal Failure and Fluid and Electrolyte Disorders
Acute Renal Failure
Disorders of Osmolality
Potassium Disorders
Acid-Base Disorders

Glomerular Renal Disease
HIV-Associated Nephropathy
Clinical Course and Treatment
Other Renal Lesions
Diagnosis and treatment

End-stage Renal Disease
Improved Survival of the HIV-Positive ESRD Patient
Infection Control in Hemodialysis
Peritoneal Dialysis
Medical Management

Table 1: Dosing of Antiretroviral Drugs in Renal Insufficiency and Hemodialysis
To view Table and discussion on HivInsite website:
Renal disorders are encountered at all stages of HIV infection, and range from fluid and electrolyte imbalances commonly seen in hospitalized HIV-infected patients, to HIV-associated nephropathy (HIVAN), which can progress rapidly to end-stage renal disease (ESRD).(1) This chapter begins with a review of acute renal failure (ARF) and fluid and electrolyte disorders, both of which are often associated with treatments for HIV-related conditions. The focus of the subsequent discussion is on the pathogenesis and treatment of HIVAN, other HIV-associated glomerular diseases, and management of ESRD.
Acute Renal Failure and Fluid and Electrolyte Disorders
Acute Renal Failure
Mild ARF, defined as a peak serum creatinine >=2.0 mg/dL, has been reported to occur in up to 20% of hospitalized HIV-infected patients.(2) This percentage compares to an incidence rate of 4-5% in hospitalized non-HIV-infected patients.(3) The two most common causes of ARF in this population are dehydration and acute tubular necrosis (ATN). A study of kidney biopsy specimens in HIV-infected patients with severe ARF not thought to be due to pre-renal causes or ATN reported the following distribution of renal lesions: 53% hemolytic uremic syndrome; 40% ATN either of ischemic-toxic origin or due to rhabdomyolysis; 26% obstructive renal failure that was either extrinsic, drug-induced, or secondary to paraprotein precipitation; 23% HIV-associated nephropathy; 3% acute interstitial nephritis; and 6% various glomerulonephritides.(4)
Common causes of ATN include sepsis, hypotension, and medications commonly used in the treatment of HIV-related infections such as aminoglycosides, pentamidine, acyclovir, foscarnet, amphotericin, tenofovir, adefovir, and cidofovir.(5) In addition to ATN, foscarnet may produce a dose-related ionized hypocalcemia, with normal total serum calcium. Foscarnet also is frequently associated with a transient hyperphosphatemia during the second week of induction therapy.(5) Similar to the renal toxicity seen with adefovir and cidofovir, tenofovir is associated with ARF, proximal tubular dysfunction, and nephrogenic diabetes insipidus. Patients with tenofovir toxicity may present with glycosuria, hypophosphatemia, acidosis, proteinuria, and ARF.(6-9) These nephrotoxic drugs must also be used with caution and dose adjusted in HIV-infected patients with chronic kidney disease or ARF.
In HIV-infected patients, sepsis contributes to the development of severe renal failure, defined as a peak creatinine >=6.0 mg/dL, in up to 75% of cases.(10) The probability for survival and recovery from the ARF is dictated by the nature and severity of the underlying illness. Severe renal failure in HIV-infected patients may be associated with terminal conditions in which acute dialysis would be inappropriate. When the acute underlying illness is reversible, however, ARF will usually reverse with dialysis and conventional supportive care.
Acute interstitial nephritis has been found in 13% of autopsies done in patients with renal dysfunction, and an inciting agent is usually not identified. Nonsteroidal anti-inflammatory drugs (NSAIDs), trimethoprim-sulfamethoxazole, and rifampin are often used in HIV-infected patients and are known to cause acute interstitial nephritis.(5,11) In addition, there have been case reports of interstitial nephritis in patients taking indinavir or ritonavir.(12,13)
Obstruction should also be considered as a cause of ARF. Sulfadiazine crystal formation causing tubular obstruction, and sulfadiazine stones causing ureteral obstruction, have been reported in volume-depleted, HIV-infected patients.(14-16) Acyclovir can also cause crystalluria and ARF, and dose adjustments should be made in patients with preexisting chronic kidney disease to avoid neurotoxicity.(17)
Roughly 4% of patients receiving the protease inhibitor indinavir may develop nephrolithiasis. Symptomatic urinary tract disease, including nephrolithiasis with renal colic, flank pain without evidence of stones, dysuria, or urgency, has occurred in 8% of patients taking the drug. Those with symptomatic urinary tract disease usually have indinavir crystalluria on urinalysis, and many have radiographic evidence of either stones or renal parenchyma filling defects. Renal failure occurs in only a minority of cases, and tends to be mild to moderate in severity. Indinavir nephrolithiasis can be prevented with ample fluid intake (1.5-2 liters per day). Symptomatic urinary tract disease may resolve with hydration alone, but in some patients recurrence of symptoms necessitates permanent discontinuation of indinavir. Asymptomatic indinavir crystalluria is found in 20% of patients and leukocyturia in 25-35% of patients receiving indinavir at the normal dose, and the drug should not be discontinued for asymptomatic crystalluria.(18) In vitro, indinavir solubility is increased at a pH of 4.5, but this is more acidic than the in vivo potential of the kidney.(19) Indinavir may also cause acute interstitial nephritis presenting with mild renal insufficiency and pyuria.(12,20)
Disorders of Osmolality
Hyponatremia has been reported in 30-60% of patients hospitalized with HIV infection.(21,22). Hyponatremia is associated with increased morbidity and mortality in HIV-infected patients.(23) Volume depletion due to diarrhea or vomiting is the usual cause of hyponatremia present at the time of hospital admission. Clinical management includes replacement of volume deficits as well as measures to treat the underlying cause of volume depletion. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the likely culprit in those who develop hyponatremia during hospitalization.(23) SIADH is usually associated with common pulmonary and intracranial diseases, such as Pneumocystis pneumonia, toxoplasmosis, and tuberculosis. The initial treatment of SIADH consists of fluid restriction and treatment of the underlying infection or malignancy. Persistent release of ADH due to infections that are slow to respond to treatment may also be managed with demeclocycline, 600-1,200 mg per day, to inhibit the action of ADH on the renal tubule. Adrenal insufficiency may also result in hyponatremia (see "Potassium Disorders" below).
Potassium Disorders
Both hypokalemia and hyperkalemia are common in HIV-infected patients. Hypokalemia is predictably seen secondary to gastrointestinal losses of potassium in HIV-infected patients with gastrointestinal infections. Amphotericin B, frequently used to treat fungal infections in patients with AIDS, can cause tubular dysfunction resulting in hypokalemia.
Drug-induced hyperkalemia is common in patients receiving either high-dose trimethoprim-sulfamethoxazole or intravenous pentamidine. The mechanism underlying hyperkalemia with both drugs consists of inhibition of distal nephron sodium transport, leading to a decrease in distal potassium secretion (similar to the action of potassium-sparing diuretics like amiloride).(24,25) Hyperkalemia and hyponatremia may also be a manifestation of mineralocorticoid deficiency due to adrenal insufficiency or the syndrome of hyporeninemic hypoaldosteronism.(26,27) Acute or chronic kidney disease may also contribute to potassium retention. Adrenal causes of hyperkalemia will often respond clinically to treatment of the underlying disorder, loop diuretics, or fludrocortisone.(27)
A systemic abnormality in potassium equilibrium, which favors the development of hyperkalemia by a mechanism unrelated to renal potassium excretion, has also been identified in HIV-infected individuals.(28)
Acid-Base Disorders
Acid-base disturbances in HIV-infected patients are commonly due to infections or drugs. Respiratory alkalosis and respiratory acidosis may occur in opportunistic infections of the lungs or central nervous system. Nonanion gap metabolic acidosis may occur as a result of several different processes, including intestinal base losses from diarrhea, or renal acidosis due to adrenal insufficiency, the syndrome of hyporeninemic hypoaldosteronism, or drug toxicity (amphotericin B).(5,26,27) High anion gap metabolic acidosis in this population results from chronic kidney disease, type A lactic acidosis due to tissue hypoxia (sepsis), and type B lactic acidosis.(29) Type B lactic acidosis presents with markedly elevated blood lactate levels possibly caused by drug-induced mitochondrial dysfunction. These patients have no evidence of hypoxemia, tissue hypoperfusion, malignancy, or sepsis. This disorder has been reported with zidovudine, didanosine, zalcitabine, lamivudine, and stavudine.(30) Although life-threatening acidosis is rare, 5-25% of treated patients may develop mildly elevated lactate levels (2.5-5 mmol/L) without acidosis. The value of screening and the predictive value of small, asymptomatic elevations in lactate, however, are unknown.(30,31)
Glomerular Renal Disease
HIV-Associated Nephropathy
HIVAN is a unique clinical and histopathologic entity, and it is thought to develop as a result of HIV gene expression in renal tissue. Proteinuria occurs in up to 30% of HIV-infected patients, but not all of these patients have HIVAN.(32-34) The true prevalence of HIVAN is not known. The geographic distribution of HIVAN is not uniform, and depends on specific risk factors for HIV disease, which include race, gender, and drug use. There is a striking predilection for HIVAN among African American individuals, as is also true for focal segmental glomerulosclerosis (FSGS) associated with intravenous drug use (IVDU).(35,36) HIVAN is 7-10 times more common in men than in women, and 30-60% of people with HIVAN have a history of IVDU.(35,36) Thus, in the United States, the typical patient with HIVAN is a young African American male with a history of IVDU. Clinical presentation typically includes proteinuria but no hematuria on urinalysis, rapidly progressive renal insufficiency, and large, echogenic kidneys.
HIVAN is associated with characteristic glomerular, tubulointerstitial, and ultrastructural lesions. The most consistent findings include collapsing focal segmental glomerular sclerosis, cystic tubular dilatation, interstitial edema, cellular infiltrates, and dilated tubules filled with pale-staining amorphous casts. Electron microscopy often reveals tubuloreticular inclusions in endothelial cells, and nuclear bodies are also noted frequently.(37,38) The ultrastructural changes are not unique to HIVAN, as they are also seen in idiopathic FSGS, heroin nephropathy, and as a rare complication of pamidronate therapy.(37,39)
The pathogenesis of HIVAN has been studied intensely over the past 15 years, and the accumulated data in humans and animal models provides substantial evidence that HIVAN is caused by HIV gene expression in renal tissue, resulting in injury of glomerular and tubular epithelial cells. Early studies using in situ hybridization to a cDNA nucleic acid probe found the HIV genome in tubular and glomerular epithelial cells in patients with HIVAN. Patients with immune-mediated glomerulonephritis or HIV-infected patients with no renal disease had less cellular involvement.(40) More sensitive PCR techniques detected DNA from the HIV genome in all renal cell types except interstitial cells in HIV-infected patients with proteinuria, but the HIV DNA was also present in kidney tissue from HIV-infected patients without renal disease.(41) However, other studies failed to confirm the presence of HIV proteins in renal tissue of patients with HIVAN.(42) The important role of HIV viral products in the pathogenesis of HIVAN has now been demonstrated in studies using transgenic mice containing a noninfective HIV construct encoding the envelope glycoproteins gp41 and gp120 but lacking the gag and pol genes. These mice develop a renal syndrome closely resembling HIVAN.(43) This transgenic mouse model was used to confirm that the renal disease develops from intrinsic factors in the transgenic kidney. Kidneys were transplanted between normal and transgenic mice. HIVAN then developed in the transgenic kidneys transplanted into the nontransgenic littermates, whereas the normal kidneys remained disease free when transplanted into the transgenic littermates. This study provides evidence that HIVAN is caused by a direct effect of HIV gene expression rather than the systemic effects of HIV infection.(44) This model also demonstrated that the HIV transgene is expressed in renal glomerular and tubular epithelial cells, and that transgene expression in renal epithelial cells was required for the development of the HIVAN phenotype.(44) In addition, of the nine HIV genes, which encode 15 proteins, nef has been shown to be necessary and sufficient to cause most of the HIV-induced changes seen in podocytes in HIVAN.(45)
Although the mechanism for HIV entry into renal cells remains unknown, recent studies in humans indicate that HIV gains entry into the epithelium and that full-length mRNA is generated.(46) HIV was detectable in renal epithelial cells by RNA in situ hybridization in 11 of 15 patients with HIVAN. In addition, HIV infection may involve epithelial cells from multiple segments of the nephron, including proximal tubule, thick ascending loop of Henle, and collecting duct. This pattern of involvement may explain the tubular dilatation seen in kidney biopsy specimens of patients with HIVAN.(47)
The kidney also seems to be a reservoir for HIV. Despite undetectable viral levels in the serum, a case report described a patient who continued to express HIV in renal epithelial cells as determined by RNA in situ hybridization.(48) There is also compelling evidence that active replication of HIV occurs in kidney epithelium, possibly producing HIV strains in the kidney microenvironment that differ from HIV circulating in the blood. This suggests that the kidney may serve as a viral reservoir harboring HIV strains that have evolved under tissue-specific selection pressures.(49)
Clinical Course and Treatment
Until recently, the clinical course of HIVAN was one of inexorable progression to ESRD in 6-12 months, with limited treatment options. More options are now available to patients, and include antiretroviral therapy, steroid treatment, and angiotensin-converting enzyme inhibitors (ACE-Is). Despite the widespread use of effective antiretroviral therapy (ART) over the last 6 years, limited evidence exists that ART can reverse or improve the progression of HIVAN. There have been case reports of dramatic improvements in renal function with the initiation of combination ART,(48,50,51) but no prospective studies have shown a benefit in the course of HIVAN. Despite the low efficacy of monotherapy with zidovudine for HIV disease, retrospective studies and case reports have suggested that zidovudine may slow or even reverse the rapid renal deterioration associated with HIVAN.(52-55) One study concluded that zidovudine is beneficial in HIVAN, but the results of this sole prospective study of the effect of zidovudine on the course of HIVAN are difficult to interpret.(56) The control group consisted of ESRD patients with possible HIVAN, a group known to have a very poor prognosis. In addition, most of the study patients had only mild proteinuria and normal renal function in the setting of HIV infection, and the natural course of renal disease in such patients is not known.(56) Moreover, only 5 of 14 patients with proteinuria had a renal biopsy to confirm the diagnosis of HIVAN. The AIDS Clinical Trials Group (ACTG) is currently developing a clinical trial (protocol A5179) to compare treatment with an angiotensin receptor blocker (valsartan) plus ART to ART alone in patients with HIVAN.
The rationale for treating HIVAN with corticosteroids is that steroids are the mainstay of treatment for idiopathic FSGS.(57) In August 1994, the first report of steroid treatment in 4 patients with HIVAN found a significant reduction in serum creatinine after a 2- to 6-week course of corticosteroids.(58) In 1995, the ACTG designed a phase II randomized, double-blind, placebo-controlled multicenter trial to determine the efficacy of prednisone therapy in HIVAN, but this trial was canceled because of poor patient recruitment. The initial case report study has now been extended to include 20 patients, and these results confirm that prednisone at a dose of 60 mg daily for 2-11 weeks leads to a significant reduction in serum creatinine and in 24-hour urinary protein excretion.(58) The encouraging short-term results must be balanced by the findings during the follow-up period. During a median follow-up of 44 weeks, 8 of 20 patients required maintenance dialysis, 11 of 20 died of HIV disease after completing prednisone treatment, and 6 of 20 developed serious infections while receiving prednisone. Only 7 of 20 patients were alive and free from ESRD after a median of 25 weeks following initiation of prednisone.(58) A more recent retrospective study reported the course of HIVAN in 13 patients treated with, and 8 patients not treated with, prednisone. Even after controlling for baseline creatinine, proteinuria, and CD4 count, among other variables, the prednisone group had an 80% reduction in risk of progressive azotemia after 3 months.(59) Prednisone may work by reducing the amount of interstitial inflammation.(60)
The ACE-Is captopril and fosinopril have also been studied as a form of therapy for HIVAN.(61) Angiotensin II increases the cellular synthesis of transforming growth factor-beta (TGF-beta ), which has been implicated in the pathogenesis of HIVAN; thus an ACE-I may protect against HIVAN by reducing production of TGF-beta .(62,63). In one study in which 18 patients were enrolled, 9 were treated with captopril, 6.5-25 mg three times daily, and 9 controls did not receive captopril. All patients had biopsy-proven HIVAN, and renal survival was defined as the time from initiation of captopril treatment to initiation of dialysis (ESRD). The initial mean serum creatinine concentration was 3.4 ▒ 0.7 mg/dL in the captopril group versus 3.7 ▒ 0.5 mg/dL in the controls. A small renal survival advantage of approximately 8 weeks (median 83 vs 30 days), was seen in the captopril group.(61) Two nonrandomized studies have investigated the effect of fosinopril on the progression of HIVAN. Both studies showed a significantly lower risk of reaching ESRD in the fosinipril group compared to nontreated controls.(64,65) Despite the limitations of these studies, they suggest that ACE-I initiated early may offer renal survival benefits in HIVAN.
Our current recommendations for treatment of HIVAN, based on the limited data available, begin with diagnosis. Renal biopsy should be offered to patients because a variety of renal lesions occur in HIV-infected patients, and the treatment implications and prognosis vary according to the biopsy results. Risk factors for progressive renal disease include CD4 count <200 cells/ÁL, detectable HIV RNA level, hypertension, low albumin, and elevated serum creatinine.(66) Combination ART should be initiated early in these patients (see chapter "Initiating Antiretroviral Therapy"). Because serum viral loads do not necessarily reflect the severity or rate of progression of HIVAN, ART should be considered in patients with less advanced HIV disease but progressive renal failure due to HIVAN.(48) The degree of renal insufficiency should influence the choice and dose of the individual antiretroviral agents (Table 1). ACE-Is should certainly be the antihypertensive drug of choice in HIV-infected patients with renal disease and hypertension, and should be considered in normotensive HIV-infected patients with renal disease. The role of corticosteroid treatment remains controversial, but may be considered in patients with HIVAN and early HIV disease whose renal failure is progressing rapidly. A discussion that includes the risks of short-term immunosuppression, the benefit of slowing the progression to ESRD, and the patient's wishes should precede the final decision regarding corticosteroid therapy.
Other Renal Lesions
HIVAN is rare in non-African Americans. In published renal biopsy reports from France, Italy, and Thailand, patients with HIV infection and renal disease usually have a variety of immune complex glomerular diseases and rarely have HIVAN.(67-69) The patterns of glomerular involvement seen in these patients include IgA nephropathy, membranous nephropathy, and membranoproliferative, mesangial proliferative, diffuse proliferative, or crescentic glomerulonephritis.(70)
Two important forms of immune complex glomerulonephritis in HIV infection are IgA nephropathy and hepatitis C virus (HCV)-related renal disease. HIV has been implicated as a stimulus for immune complex formation in IgA nephropathy; immune complexes with HIV antigens have been identified in the circulation and renal tissue eluates of HIV-infected patients with IgA nephropathy and with immune complex glomerulonephritis.(70,71) HCV-associated cryoglobulinemic glomerulonephritis has been well described in both HIV-infected and uninfected patients, and is characterized by membranoproliferative glomerulonephritis, purpura, arthralgias, and peripheral neuropathy.(72,73) Cryoglobulinemia that is clinically significant (ie, causing glomerulonephritis or purpura) is now known to be almost exclusively associated with HCV infection. The risk for HCV coinfection in HIV patients is associated with particular routes of exposure; the incidence of HCV is as high as 90% in patients with a history of IVDU.(74,75) The renal presentation of HCV in HIV/HCV-coinfected patients may include renal insufficiency, proteinuria, hematuria, depressed complement levels, and circulating cryoglobulins. The course of HCV-associated renal disease is much more aggressive in the coinfected patient, with some progressing to ESRD in a matter of months.(73,76)
In non-HIV-infected patients, the association of membranous nephropathy with hepatitis B virus (HBV), malignancy, and syphilis has also been well described, and the reports of membranous nephropathy in HIV-infected patients may be explained by the high incidence of HBV infection, malignancies, and syphilis in this population.(67,75,77-80).
Other renal diseases reported less commonly in HIV-infected patients include minimal change disease, amyloidosis, hemolytic uremic syndrome, and tumor invasion of the kidneys.(11,81,82)
Diagnosis and treatment
The evaluation of an HIV-infected patient with glomerular renal disease characterized by proteinuria and normal or elevated creatinine should start with excluding possible secondary causes of glomerular disease. The history and physical examination and serologic tests should focus on evidence for malignancy, HCV, HBV, or syphilis. Short of a kidney biopsy, it is very difficult to distinguish HIVAN from the other glomerular diseases. The results of the kidney biopsy should guide therapy. For example, membranoproliferative glomerulonephritis with evidence of HCV coinfection may necessitate treatment of the HCV. Treatment of the immune complex glomerulonephritides should be directed toward the associated coinfection or malignancy, if present. If immune complex glomerulonephritis is present on kidney biopsy specimen, but no coinfection or malignancy is diagnosed, HIV infection may be the etiology of the immune complex glomerulonephritis, and the course of the renal disease will probably be benign or may respond to ART.
End-stage Renal Disease
The U.S. Renal Data System (USRDS) reported that from 1993 to 1997, there were 3,629 incident cases of ESRD in HIV-infected patients.(83) Almost all of these cases (>90%) occurred in African Americans. HIVAN has become the third leading cause of ESRD among African Americans aged 20-64 years.(1) Management of ESRD in the HIV-infected patient poses specific medical and logistical challenges to dialysis care providers. Hemodialysis, peritoneal dialysis, and transplantation are options for these patients, and each modality has advantages and disadvantages.
Improved Survival of the HIV-Positive ESRD Patient
Early studies from the 1980s reported that newly diagnosed patients with ESRD and AIDS were dying an average of 1-3 months after starting hemodialysis.(35) Based on this observation, some nephrologists argued that dialysis should be restricted in this population. These early studies predominantly included patients late in the course of the HIV disease with advanced opportunistic infections. Nevertheless, ART-associated improvements in the survival of HIV patients without ESRD have translated into only modest improvements in the survival of ESRD patients with HIV infection.(84) Even prior to the availability of effective ART, several groups reported improved survival in subgroups of HIV-infected dialysis patients with higher CD4 counts.(85,86) In the general HIV-infected population, ART has led to dramatic improvements in survival. However, the improvement in survival seems to be attenuated in HIV patients with ESRD.(87) Among HIV-infected patients dialyzed between 1985 and 2002 at San Francisco General Hospital, survival was 33.4 months for patients with CD4 cell counts above 200 cells/ÁL compared to 7.7 months for patients with CD4 cell counts below 200 cells/ÁL. Currently there is no reason to withhold renal replacement therapy from patients solely on the basis of HIV infection.(87)
The most common renal replacement modality for HIV-infected patients is hemodialysis. Potential disadvantages of hemodialysis include risk of infections from temporary catheters and grafts, and risk to dialysis providers of blood and needlestick exposure. A 1992 study showed that synthetic graft infection rate was 43% in patients with AIDS, 36% in patients with asymptomatic HIV infection, and 15% in patients who were HIV negative (p < .05).(88) Subsequent studies have shown that thrombus-free survival for native arteriovenous fistulas in HIV-positive patients is comparable to that reported for HIV-negative patients.(89) Because the progression of HIVAN to ESRD is typically quite rapid, HIV-positive patients with chronic kidney disease who have chosen hemodialysis over peritoneal dialysis should be referred early to a nephrologist and to a surgeon for placement of a native arteriovenous fistula.
Infection Control in Hemodialysis
Careful adherence to universal body substance precautions must be followed by dialysis providers treating HIV-infected ESRD patients. HIV-infected patients do not require special isolation precautions during dialysis, and dialyzer-reuse programs are permissible in HIV-infected patients. Routine infection-control precautions and routine cleaning with sodium hypochlorite solution of dialysis equipment and of surfaces that are frequently touched are sufficient in HIV-infected patients on hemodialysis. Precautions such as isolation of HIV-infected patients from other dialysis patients are unnecessary and could violate medical confidentiality.
Dialysate should be treated as a potentially contaminated body fluid. The size of the HIV particle is much larger than most dialyzer membrane pore sizes; therefore, the HIV particle most likely does not cross the dialyzer membrane into the dialysate or ultrafiltrate. Despite a small decrease in plasma HIV RNA levels during hemodialysis, one study could not measure HIV RNA in the ultrafiltrate of 10 HIV-infected hemodialysis patients.(90) However, there are little data concerning HIV in dialysate, especially in dialyzers that are being reused.
Peritoneal Dialysis
Although potential exposure by contaminated blood or needles to dialysis personnel is not a problem with peritoneal dialysis, peritoneal protein losses in malnourished HIV patients and severe peritonitis are potential concerns.
The incidence and spectrum of peritonitis has been reported in several small series of HIV-infected patients. The largest series studied 39 HIV-infected patients on peritoneal dialysis and found a higher overall risk of peritonitis and more peritonitis attributed to Pseudomonas species and fungi than in other ESRD patients.(85,86) It was not clear from this study whether the higher peritonitis rate was due to HIV infection or to confounding variables such as low socioeconomic status and IVDU. In terms of survival, these studies suggest that peritoneal dialysis is equivalent to hemodialysis in HIV-infected patients.(85,86)
HIV has been identified in peritoneal dialysate fluid, which should be handled as a contaminated body fluid.(91) Peritoneal dialysis patients should be instructed to pour dialysate into the home toilet, and to dispose of dialysate bags and lines by tying them in plastic bags and disposing of the plastic bags with conventional home garbage.
Medical Management
The standard Dialysis Outcome Quality Initiative (DOQI) recommendations should be followed for HIV-infected patients with ESRD.(91) As noted above, native A-V fistulas are optimal in these patients to reduce the incidence of catheter and graft infections. The goals for dialysis dose (dialysate flow x treatment time/anthropometric volume [Kt/V]), renal osteodystrophy and anemia management, and vascular access monitoring should be followed as outlined in the DOQI recommendations. HIV-infected patients with ESRD respond well to erythropoietin therapy.
Coinfection with HCV is very common in HIV-infected ESRD patients. Optimal therapy for HCV infection in the ESRD patient is not known, especially as ribavirin is not recommended in patients with renal failure. At a minimum, HIV/HCV-coinfected patients should be discouraged from alcohol use and should be vaccinated for hepatitis A and B virus. In the absence of ESRD, HIV-infected patients have an 88% antibody response rate to hepatitis A virus vaccine, but only a 42% response to hepatitis B virus vaccine.(92,93)
Recent improvements in the survival of HIV-infected patients are due not only to ART but also to improved prophylaxis for and treatment of opportunistic infections. Several antiretroviral drugs are excreted primarily through the kidney and must be dose adjusted in the setting of renal insufficiency or hemodialysis. Table 1 summarizes antiretroviral drug doses for patients with impaired renal function.
The nucleoside and nucleotide analogue reverse transcriptase inhibitors require dose adjustment in patients with renal insufficiency. Although there are little data on the pharmacokinetic properties of the nonnucleoside reverse transcriptase inhibitors and protease inhibitors in patients with renal insufficiency, the pharmacokinetic profiles of these drugs suggest a minimal effect of renal function on drug elimination.
Table. Dosing of Antiretroviral Drugs in Renal Insufficiency and Hemodialysis (see link at beginning of the article to view tables)
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