Late recurrence of lupus nephritis in a renal transplant recipient: response to mycophenolate mofetil.

Clinically significant recurrence of lupus nephritis in the renal allograft is low, with an incidence of 1 to 3%, and usually occurs within the first 6 years after transplantation. We report an unusual case of a patient with end-stage renal disease caused by lupus nephritis who received a kidney transplant from a living relative; 13 years later, the patient had a severe recurrence of diffuse proliferative lupus nephritis. The patient relapsed after receiving intravenous cyclophosphamide therapy and had a partial response to oral mycophenolate mofetil. In this report we review the risk factors for the recurrence of the systemic lupus erythematosus in the kidney graft and the anti-lupus activity of mycophenolate mofetil.

Prevalence of glomerulopathies in autopsies of patients infected with the hepatitis C virus.

BACKGROUND: Several reports have shown hepatitis C virus (HCV) infection to be associated with various extrahepatic manifestations, including certain forms of glomerulopathy. The most frequently reported glomerulonephritis in patients infected with HCV is either membranoproliferative glomerulonephritis (MPGN) or cryoglobulinemic glomerulonephritis, and HCV has been directly implicated in their pathogenesis. Other investigators have reported a higher prevalence of HCV infection in patients with membranous glomerulonephritis, IgA nephropathy, and focal segmental glomerulosclerosis (FSGS). However, the prevalence of these glomerulopathies in patients infected with HCV is unknown. METHODS: We conducted a 5-year retrospective review to determine prevalence of glomerulopathies in autopsies of patients infected with HCV. The renal histology on the autopsy reports was carefully reviewed for appropriate diagnosis of glomerulonephritis. RESULTS: Of the 114 autopsies of patients infected with HCV during this period, the majority had been incarcerated and had state-mandated autopsies. The mean age of the patients was 46.8 +/- 10 years (+/- SD; range, 19-87). Of the 114 patients, 46 were white, 37 were African American, and 31 were Hispanic. The glomerulopathies seen were 3 MPGN, 2 membranous, 3 HIV-associated nephropathy, 1 idiopathic FSGS, 1 minimal change glomerulonephritis, and 3 diabetic nephropathy. CONCLUSION: We conclude that although HCV is reported to be associated with membranoproliferative and membranous glomerulonephritis, their prevalence in these patients is not common.

Predictors of the development of hyperkalemia in patients using angiotensin-converting enzyme inhibitors.

BACKGROUND/AIMS: Angiotensin-converting enzyme inhibitors (ACEI) are the antihypertensives of choice in patients with chronic renal failure (CRF). ACEI by decreasing the synthesis of aldosterone, the main regulator of serum potassium, predispose to the development of hyperkalemia. Although hyperkalemia with administration of ACEI is uncommon in patients with a normal renal function, a preexisting abnormality in potassium hemostasis, as seen in patients with chronic renal failure, may increase the risk of hyperkalemia. METHOD: To determine the predictors of development of hyperkalemia (K >5.1 mEq/l) in patients on ACEI, we retrospectively reviewed medical records of 119 patients followed in our renal clinic. RESULTS: The mean age of the patients was 56 +/- (SD) 13 (range 20-84) years. Sixty-three percent were males, and 37% were females. Sixty-seven percent had a history of diabetes. Eighty five percent of the patients had CRF [creatinine clearance (CrCl) <80 ml/min]. The baseline serum Cr was 2.3 +/- 1.2 (range 0.6-6.9) mg/dl, and the CrCl was 50 +/- 27.5 ml/min. Of the 119 patients 46 (38.6%) developed hyperkalemia (mean K 5.68 +/- 0.3, range 5.2-6.7 mEq/l). Ninety-six percent of the patients who developed hyperkalemia had CRF, and 84% were diabetics. Pearson product-moment correlation revealed a significant positive correlation of hyperkalemia with Cr and a negative correlation of hyperkalemia with CrCl and HCO(3) (Cr: r = 0.42, p < 0.0001; CrCl: r = -0.34, p < 0.0001; HCO(3): r = -0.41, p < 0.0001). Multivariate logistic regression analysis revealed diabetes and serum creatinine to be the main predictors of hyperkalemia. In 31 patients hyperkalemia resolved either with a low-potassium (2 g/day) diet or with diet and a decrease in the dose of ACEI. In 15 patients ACEI had to be discontinued due to persistent hyperkalemia. CONCLUSIONS: We conclude that hyperkalemia is common in patients with CRF on ACEI. The majority of the patients who develop hyperkalemia on ACEI have CRF and diabetes. A large number of patients with CRF require discontinuation of ACEI due to hyperkalemia and are deprived of their renoprotective effects.

Highly active antiretroviral therapy improves survival of HIV-infected hemodialysis patients.

Human immunodeficiency virus (HIV)-infected hemodialysis (HD) patients have a very high morbidity and mortality. Reports from the last few years have suggested that highly active antiretroviral therapy (HAART) has remarkably improved the survival of HIV-infected patients. To determine whether the beneficial effects of HAART have also extended to HIV-infected HD patients, we retrospectively evaluated the survival of all HIV-infected patients who underwent chronic maintenance HD between 1992 and 1999 at our institution. Twenty-two HIV-infected patients were started on chronic maintenance HD at our institute during this period. The mean age of the patients was 36 +/- 9 (SD) years (range, 21 to 58 years). Seven patients were treated with only one or two antiretroviral drugs (patients 1 and 5 were administered two antiretroviral drugs), and the remaining 15 patients were treated with HAART (three antiretroviral drugs or more). Fifty-seven percent (4 of 7 patients) of the patients on suboptimal therapy died after a mean time on HD therapy of 13 +/- 10 months compared with only 20% (3 of 15 patients) of those on HAART after a mean period on HD therapy of 28 +/- 17 months. Plasma viral load was significantly less in patients on HAART compared with patients on suboptimal therapy (3.35 +/- 0.92 versus 4.63 +/- 1.3 log(10) copies/mL; P = 0.03). Patients with diagnoses other then HIV-associated nephropathy and those on HAART had statistically longer survival times (P = 0.02 and P = 0.04, respectively). We conclude that HAART is successful in suppressing viral load in HIV-infected HD patients, and the survival of HIV-infected HD patients on HAART is better than that of patients on suboptimal antiretroviral therapy.

Contrast-induced nephrotoxicity in renal allograft recipients.

BACKGROUND: Intravenous administration of radiographic contrast agents is an important cause of acute renal failure, accounting for one third of the cases of hospital-acquired acute renal failure in patients with native kidneys. The safety of intravenous contrast has not been studied in renal allograft recipients since the availability of cyclosporine as a maintenance immunosuppressive therapy. As patients with renal transplantation may be at a higher risk of contrast-induced nephrotoxicity (CIN) due to concomitant use of cyclosporine and higher prevalence of diabetes and renal insufficiency, we retrospectively studied development of CIN in these patients. PATIENTS AND METHODS: We identified 44 patients (1988 1997) with functioning renal allograft who underwent different intravenous or intraarterial contrast studies (ICS). Pre- and post-ICS renal function tests were done in 35 of these patients. The following were the various ICS done in these patients: coronary angiogram (6), CT scan with intravenous contrast ( 11), angiogram for evaluation of peripheral vascular disease (11), allograft angiogram with angioplasty (5), pulmonary angiogram (1) and intravenous pyelogram (1). The mean age of the patients was 42 +/- 2.1 years and the mean serum creatinine was 2.3 +/- 0.25 mg/dl (mean +/- SEM). Fourty percent of patients (14 of 35) had diabetes, and 25.7% (9 of 35) had chronic rejection. Ninety four percent (33 of 35) of the patients were taking cyclosporine at the time of ICS. RESULTS: Nine patients had > or = 25% increase in serum creatinine from baseline after ICS. Two of these patients were excluded from the analysis as renal functions in these patients had deteriorated prior to ICS and renal failure was attributed to sepsis. Of the remaining 7 patients, 5 had diabetes and 2 had chronic rejection. Only 4 of these 7 patients with CIN received prophylaxis (I/V hydration) prior to ICS. The baseline serum creatinines were not different in patients who had no change in renal function to those who developed CIN (1.97 +/- 0.20 vs 1.54 +/- 0.17 mg/dl, p = 1.5, mean +/- SEM). More than 50% increase in baseline serum creatinine was seen in only 3 of these 7 patients, 2 of these patients had diabetes and third had chronic rejection and congestive heart failure. None of these patients received prophylaxis for CIN. Dialysis was not required in any patient. Three patients also had a > 25% decrease in baseline serum creatinine after ICS, and all of them had allograft angiography with angioplasty for renal artery stenosis. CONCLUSION: In our retrospective study, the incidence of CIN in renal allograft recipients applying a broader classification of > or = 25% increase in baseline serum creatinine was 21.2% (7 of 33 patients). The incidence of CIN was lower 15.3% (4 of 26) in patients who received intravenous hydration compared to 42.8% (3 of 7) in patients who received no prophylaxis prior to ICS.

Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients.

Previous studies have reported that approximately 10% of the patients with human immunodeficiency virus (HIV) infection develop HIV-associated nephropathy (HIVAN). However, over the last decade, morbidity and mortality as a result of HIV-1 infection has remarkably decreased with the availability of potent new antiretroviral drugs. We therefore determined the prevalence of HIVAN from autopsy data of HIV-infected patients in more recent years (1992 to 1997). Autopsy reports of 389 patients were reviewed. In reports suggestive of possible HIVAN, slides of renal tissue were retrieved and reviewed again to ensure appropriate classification. The criteria for the diagnosis of HIVAN were focal segmental glomerulosclerosis with collapse of the glomerular tuft in some glomeruli, extensive tubular ectasia, and significant tubulointerstitial disease. Of 389 autopsy reports, 54% of the patients were black, 35% were white, and 11% were Hispanic. Thirty-three percent of the patients had a history of intravenous drug abuse. The mean CD4 count of the patients was 54 +/- 91/microL (mean +/- SD). In 27 cases, typical features of HIVAN were found based on the criteria used, accounting for an overall HIVAN prevalence of 6.9% (27 of 389 autopsies). Because the overwhelming majority of these patients were black (93%), the prevalence in blacks was 12% (25 of 209 autopsies). We conclude that although mortality and morbidity from HIV infection is decreasing, HIVAN remains an important complication of HIV infection in blacks, even in recent years.

Is the prevalence of HIV-associated nephropathy decreasing?

Initial reports have suggested that approximately 10% of patients with HIV-infection develop HIV-associated nephropathy (HIVAN). It has also been predicted that by the end of the decade, HIVAN is likely to become a third leading cause of end-stage renal disease (ESRD) in African-Americans between the ages of 20-64 years. As the morbidity and mortality from HIV-infection has decreased in the last few years, it is possible that prevalence of HIVAN is also changing. We therefore screened HIV-1-infected patients followed in our hospital for HIVAN. A screening urinalysis was performed in 557 HIV-1-infected adult patients between March and May 1998. Of these, 252 were outpatients and 305 were Texas Department of Criminal Justice inmates (TDCJI). Demographic and laboratory data of these patients was obtained from the HIV patients' database. Fifty percent of the patients were African-American, 36.6% were Caucasian and 12. 7% were Hispanic. The mean age of patients was 37 +/- 8 years. Seventy-nine percent of the patients were males and a history of intravenous drug abuse (IVDA) was present in 28%. Twenty-three percent of the patients were concomitantly infected with hepatitis C virus, 4.1% were positive for hepatitis B surface antigen, and rapid plasma reagin test for syphilis was positive in 9.1%. In 38 patients who had more than 100 mg/dl (2+) proteins on screening urinalysis, total urinary proteins were quantitated by collecting 24 h urine specimens. Fifteen of these patients had urinary proteins more than 1.5 g/day (12 patients >3.5 g/24 h and 3 patients >1.5 g/24 h). A renal biopsy was done in 14 of these patients and clinical diagnosis of HIVAN was made in one patient who refused biopsy. Renal biopsies revealed HIVAN [9], diabetic nephropathy [2], membranoproliferative glomerulonephritis [2], Fibrillary glomerulonephritis [1]. All 10 patients (5 TDCJI and 5 outpatients) with HIVAN were African-American. Two of these 10 patients had a history of IVDA and another two were concomitantly infected with hepatitis C virus. The plasma viral load (Pvl) and total CD4 count was not different in patients with or without HIVAN [(Pvl log 10.05 +/- 1.39 vs. 9.9 +/- 2.18 copies/ml, p = 0.78) (CD4: 187 +/- 192 vs. 288 +/- 249 cells/microl, p = 1.17) mean +/- SD]. We conclude that in our HIV-infected population HIVAN exclusively affected African-Americans and the prevalence in them was 3.5%.

Rhabdomyolysis associated with near-drowning.

A variety of conditions can lead to rhabdomyolysis. Only a few cases of rhabdomyolysis resulting from near-drowning exist in the literature. We describe a victim of near-drowning who developed rhabdomyolysis and acute renal failure requiring dialysis. We review the existing literature on near-drowning-induced rhabdomyolysis and discuss the possible pathogenesis.

Effect of hemodialysis and antiretroviral therapy on plasma viral load in HIV-1 infected hemodialysis patients.

BACKGROUND: Plasma viral load has become an important test in predicting the progress of HIV-1 infected patients. The higher the viral load the faster is the progression to AIDS. As HIV-1 infected hemodialysis (HD) patients have higher mortality and morbidity than HIV-1 infected non-dialysis patients, and as all the blood tests in the HD patients are drawn during HD, we measured the effect of HD and antiretroviral therapy on viral load in HIV-1 infected HD patients. PATIENTS AND METHODS: We measured plasma viral load pre-dialysis and post-dialysis in 10 HIV-1 infected HD patients. The viral load was measured using an in vitro quantitative nucleic acid amplification test. We also compared viral load in 8 HIV-1 infected HD patients on one antiretroviral drug with 8 HIV-1 patients on two (6) or three (2) antiretroviral drugs. RESULTS: There was a small reduction in plasma viral load postdialysis in all HIV-1 infected HD patients (45% +/- 5.4, 0.3 log +/- 0.05, p < 0.0004). However, HIV-1 RNA could not be detected in the ultrafiltrate. The patients who were on two or three antiretroviral drugs had lower viral load (8915 +/- 3702 vs. 351440 +/- 101237, p < 0.004) and higher CD4 count (355 +/- 81 vs 82 +/- 39, p < 0.009) than patients on only one antiretroviral drug. CONCLUSION: We conclude that there is a small reduction in plasma viral load in HIV-1 infected hemodialysis patients post-dialysis. As no viral RNA could be detected in the ultrafiltrate, the reduction could be due to nonspecific adsorption of the viral RNA to the dialysis membrane. HIV-1 infected hemodialysis patients who are on two or three antiretroviral drugs had significantly lower viral load and higher CD4 count than patients on only single antiretroviral drug. Therefore a single antiretroviral drug should not be used in treating HIV-1 infected HD patients.

IgA nephropathy in psoriasis.

IgA nephropathy (IGAN) was first described by Berger and Hinglais in 1968. It is now the most common glomerular disease worldwide. IGAN has been associated with several diseases. Its association with psoriasis has been rarely described. We report a case of IGAN with crescentic changes, associated with psoriasis vulgaris. We review the literature on the association of IGAN with psoriasis and discuss the likely pathogenetic linkage.

Diabetic nephropathy with anti-GBM nephritis.

Immune complex glomerulonephritis can be superimposed on diabetic glomerulosclerosis. Idiopathic membranous glomerulonephritis, immunoglobulin (Ig) A glomerulonephritis, Henoch-Schönlein nephritis, membranoproliferative glomerulonephritis, minimal change glomerulonephritis, postinfectious glomerulonephritis, lupus nephritis, amyloidosis, focal segmental glomerulosclerosis, and rarely crescentic glomerulonephritis can all occur with diabetic nephropathy. We describe for the first time an unusual case of diabetic nephropathy coexistent with anti-glomerular basement membrane (GBM) nephritis. The renal function of this patient improved with plasmapheresis and immunosuppressives. We also review the literature on coexistent rapidly progressive glomerulonephritis (RPGN) and diabetic nephropathy.

Acute renal failure in a patient with AIDS: histoplasmosis-induced granulomatous interstitial nephritis.

Although the most frequent cause of acute renal failure (ARF) in patients with AIDS is acute tubular necrosis (ATN) secondary to ischemic renal injury from septicemia, a spectrum of causes may result in ARF in these patients. We report a patient with AIDS who developed ARF and was found to have granulomatous interstitial nephritis as a result of disseminated histoplasmosis. Histoplasma capsulatum was seen in the interstitium of the kidney on renal biopsy. The patient was treated with amphotericin B and itraconazole. Although he continues to require hemodialysis 3 months after his initial presentation, his other presenting symptoms have resolved with antifungal therapy. We also discuss the literature on disseminated histoplasmosis and renal failure.

Reversible hemiplegia as a consequence of severe hyperkalemia and cocaine abuse in a hemodialysis patient.

Severe hyperkalemia may cause weakness that typically is ascending and symmetric. In an isolated case report, hemiplegia occurred after the development of hyperkalemia in a patient with a known central nervous system lesion. We describe a patient requiring long-term hemodialysis who had near-fatal hyperkalemia, hemiplegia, and rhabdomyolysis after abuse of crack cocaine. The hemiplegia resolved after normalization of serum potassium using emergency dialysis. No brain lesion could be identified during computed tomography or by electroencephalography, and the patient had no residual neurologic deficits. We conclude that this patient had hemiplegia secondary to cocaine-induced cerebral vasoconstriction because no structural lesion could be found and that the neurologic deficit was worsened by severe hyperkalemia, which probably resulted from cocaine-induced rhabdomyolysis. Hence, despite the absence of a structural lesion of the brain, severe hyperkalemia, typically associated with symmetric, ascending muscle weakness, may contribute to causing focal weakness in the condition of cocaine-induced vasoconstriction.

AIDS-associated membranous nephropathy with advanced renal failure: response to prednisone.

We report the case of a patient with acquired immunodeficiency syndrome (AIDS) who developed nephrotic syndrome and progressive renal failure mimicking human immunodeficiency virus (HIV)-associated focal segmental glomerulosclerosis (FSGS) who required initiation of hemodialysis and was found on renal biopsy to have membranous nephropathy. Hepatitis B and C serologies were negative. Although she required hemodialysis, she was treated with prednisone and experienced a progressive decline in her serum creatinine from 10.1 mg/dL to 1.9 mg/dL, which permitted the discontinuation of hemodialysis. After she abruptly discontinued prednisone, her creatinine level increased to 4.8 mg/dL, and she experienced marked worsening of her nephrotic syndrome. Resumption of prednisone resulted in normalization of serum creatinine and reduction in urine protein excretion. No adverse effects of prednisone occurred during this time. She remains off of hemodialysis for 1 year with a serum creatinine level of 1.0 mg/dL and urine protein excretion of 0.4 g/d. Although most patients with HIV infection, nephrotic-range proteinuria, and renal failure have FSGS, a minority may have membranous nephropathy. Although typically not a steroid-responsive lesion in the setting of advanced renal failure, membranous nephropathy may be a highly steroid-responsive lesion in the HIV-infected patient, and treatment may help avert the need for dialysis in a patient population that generally has a poor outcome on dialysis.

Long-term survival in an HIV-infected renal transplant recipient.

A 46-year-old Hispanic male with a history of intravenous drug abuse and sexual promiscuity received a cadaveric renal transplant in January 1984. He tested positive for HIV- 1 in February 1986. Infectious complications began 19 months after transplantation and were managed successfully until his death from sepsis 109 months posttransplant. Other HIV-infected long-term solid organ transplant survivors are reviewed from the literature. The effects of prednisone and cyclosporine on HIV- 1 expression are discussed briefly.

Wegener's granulomatosis followed by development of sarcoidosis.

Although both Wegener's granulomatosis and sarcoidosis are considered granulomatous disorders, their clinical courses differ markedly, and typically patients with these two diseases are readily distinguishable. We report an unusual case in which the patient presented with a systemic vasculitis consistent with Wegener's granulomatosis that remitted with therapy and then, months later, developed sarcoidosis. This is the first case report of the sequential development of the two diseases. We review the relationship of vasculitis to sarcoidosis and speculate on the etiopathogenesis that might link the two.

Native and oxidized low density lipoproteins modulate mesangial cell apoptosis.

Hyperlipidemia has been demonstrated to contribute to hypercellularity of the mesangium in experimental animal models of glomerulosclerosis. We studied whether it also has the potential to convert a hypercellular mesangium into a hypocellular one by inducing mesangial cell (MC) apoptosis. Low density lipoprotein (LDL) enhanced (P < 0.001) mouse mesangial cell (MMC) proliferation at lower concentrations (control, 10.3 +/- 0.3 vs. LDL 100 micrograms/ml, 24.2 +/- 0.3 x 10(4) cells/ml) but augmented (P < 0.001) apoptosis at higher concentrations (control, 5.6 +/- 0.5% vs. LDL, 500 micrograms/ml 26.2 +/- 3.4% apoptotic cells/field). Oxidized (OX) LDL enhanced MMC apoptosis in concentrations of 50 to 200 micrograms/dl. There was a direct relationship between MMC apoptosis and oxidation of LDL as judged by measuring thiobarbituric acid reactive species (TBARS). Since superoxide dismutase (SOD) attenuated (P < 0.001) LDL-induced MMC apoptosis, it seems to be mediated through the generation of free radicals by mesangial cells (control, 4.3 +/- 1.5%; LDL, 200 micrograms/ml, 19.4 +/- 0.5%; LDL + SOD, 8.1 +/- 1.3% apoptotic cells/field). LDL also induced a similar effect on human mesangial cells. These studies were further confirmed by DNA fragment assays and ELISA for programmed cell death. LDL treated cells also showed enhanced mRNA expression for RSG-2, a marker for active cell death. These in vitro results provide a basis for the speculation that LDL has the potential to cause an initial hypercellular and subsequent hypocellular mesangium in the course of the development of glomerulosclerosis.