The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis.

BACKGROUND: Acute interstitial nephritis has been known as a complication of mainly streptococcal infection for nearly a century. With the advent of infection control, it became a complication caused by antibiotics and later by other drugs, which might have changed the outcome. To determine risk factors for the development of chronic renal insufficiency, and thus, the transition from acute to chronic interstitial nephritis, we performed a retrospective study of all cases of acute interstitial nephritis found by reviewing 1,068 renal biopsies from 1968 to 1997. METHODS: Patients with permanent and reversible renal insufficiency after acute interstitial nephritis were compared with respect to the causative event, the symptoms, and the clinical and histological findings. Differences between the groups were calculated by applying bi- and multivariate analysis. RESULTS: Acute interstitial nephritis was found in 6.5% of all biopsies (64 patients with 68 episodes of acute interstitial nephritis); it was infection-induced in 10%, idiopathic in 4%, and drug-induced in 85% of the cases (antibiotics in 13 cases, analgesics in 17, non-steroidal anti-inflammatory drugs (NSAIDs) in 16, diuretics in 5, and various other drugs in 7). Renal insufficiency was reversible in 69% and permanent in 31% (12% partially reversible, 19% irreversible). The infection-induced and idiopathic types of acute interstitial nephritis were always reversible. Drug-related acute interstitial nephritis caused permanent renal insufficiency in 36% with a maximum of 56% in NSAID-induced cases. In drug-induced cases, intake of the suspected drug for more than a month prior to diagnosis caused permanent renal insufficiency in 88% and interstitial granuloma in 31%. Multivariate analysis disclosed the following significant features separating the permanent from the reversible renal insufficiency group: patients in the first group had more tubular atrophy in their histology, more chronic use of mixed analgesics and/or NSAIDs, less oliguria or anuria as an acute symptom, fewer antibiotics as causative agents, more interstitial granuloma, more pronounced interstitial cell infiltration in their histology, and more imaging of renal shrinkage. Renal histology had the highest predictive value. CONCLUSION: Today, acute interstitial nephritis is mainly drug-induced. NSAIDs are the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Clinically, subacute symptoms, a prolonged intake of the suspect drug, and chronic analgesic or NSAID use are related to a more chronic course of interstitial nephritis. In histology, tubular atrophy, interstitial granuloma, and pronounced interstitial cell infiltration indicate chronicity.

Immunotactoid-like glomerulopathy with massive fibrillary deposits in liver and bone marrow in monoclonal gammopathy.

At autopsy, massive nonamyloid fibrillar deposits, immunoreactive to IgG and kappa light chain, were found in glomeruli, liver, and bone marrow of a 72-year-old woman. The patient suffered from severe nephrotic syndrome, hepatomegaly and cholestasis, normochromic anemia, and IgG kappa monoclonal gammopathy. Fibrillary glomerulopathies, most often denoted as fibrillary glomerulonephritis or immunotactoid glomerulopathy, are generally considered to have deposits restricted to the glomeruli. However, this study indicates that fibrillary deposits may be a systemic manifestation of fibrillary glomerulonephritis or immunotactoid glomerulopathy, at least when the patient is suffering from a monoclonal gammopathy.

Impact of de novo membranous glomerulonephritis on the clinical course after kidney transplantation.

Besides rejection-induced transplant glomerulopathy de novo membranous glomerulonephritis (MGN) is the most frequent cause of nephrotic syndrome after renal transplantation. We evaluated 1029 renal transplantations (271 without and 758 with cyclosporine treatment), performed on 848 patients between 1970 and 1992, which resulted in 872 functioning grafts. De novo MGN was seen in 30 biopsy specimens from 21 patients (about 2%), of whom 10 had received immunosuppressive treatment without and 11 with cyclosporine. Taking into account the longer periods of observation of patients without compared with those with cyclosporine treatment (88 +/- 60 vs. 41 +/- 31 mo., respectively, P = 0.001), the two treatment groups did not differ significantly in prevalence of de novo MGN (4.0% vs. 1.5%). De novo MGN was diagnosed by biopsy 62.7 +/- 44.4 mo. after transplantation; its incidence increased significantly with time (from 0% to 5.3% over 8 years; 95% confidential interval: 1.7-8%). Proteinuria (mean, 3.2 +/- 2.9 g/L) was first observed 47.5 +/- 51.3 mo. after transplantation. Thirteen of the 21 patients (62%) were nephrotic (proteinuria, over 1.5 g/L). Steroid pulses were given to 12 patients with de novo MGN and high proteinuria, which did not decline after treatment. Signs of chronic viral infection (hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody) were found in 8 of the 21 patients (38%). Signs of vascular or interstitial rejection were seen in 17 and 12 of the 21 patients with de novo MGN, respectively, and cyclosporine arteriolopathy was diagnosed in four. Graft loss occurred in 14 of the 21 patients and was due to rejection in 13 and to de novo MGN in only one, who developed additional transplant vein thrombosis. Patients with de novo MGN did not differ significantly from the other 851 patients in graft survival (71.4 +/- 9.9% vs. 60.8 +/- 2.2% after 5 yr). De novo MGN is a late, often asymptomatic, complication of initially well tolerated grafts and is neither prevented by cyclosporine treatment nor reversed by further steroid medication. It is often associated with vascular changes caused by rejection or cyclosporine toxicity.

The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation--data on four cases and review of the literature.

Two women and two men were infected with the human immunodeficiency virus type 1 (HIV-1) transmitted by renal transplantation from i.v. drug-addicted donors in 1984. The four recipients were treated with cyclosporine and methylprednisolone (one patient only for three months because of early graft failure). Two patients died 66 and 74 months after transplantation, one of endocarditis and one of cerebral hemorrhage. Despite several infections including urinary tract infection (n = 8), peritonitis (n = 1), shunt infection (n = 1), bronchitis (n = 1), salmonellosis (n = 1), herpes stomatitis (n = 2), herpes zoster (n = 1), and cytomegalovirus (n = 1), and despite treatment of several rejection episodes (n = 8), none of them had or has infections typical of the acquired immunodeficiency syndrome (AIDS). However, two patients developed cervical lymphadenopathy and one autoimmune thrombocytopenia 15-20 months after HIV-1 infection. Their T helper cell counts (355/microliters to 75/microliters) and helper/suppressor T cell ratios (1.0-0.2) are distinctly lowered. One patient has membranous glomerulopathy with virus-like particles within and on the outside of the basement membrane and tubuloreticular inclusions in glomerular endothelial cells. We evaluated the case reports of 53 patients with HIV-infection caused by an infected transplant or by blood transfusions during or shortly after transplantation. The cumulative incidence of AIDS was significantly lower in 40 transplant patients with an immunosuppressive regimen including cyclosporine than in 13 transplant patients receiving immunosuppressive treatment without cyclosporine (5-year cumulative risk of AIDS: 31% versus 90%, P = 0.001).

Long-term effects of steroid withdrawal in kidney transplantation.

The long-term graft function after withdrawal of steroids from maintenance immunosuppression was analyzed in 98 kidney recipients (59 on cyclosporin monotherapy, 39 on cyclosporin plus azathioprine) who had not developed an early rejection episode when prednisolone was discontinued. Seven years after steroid withdrawal the probability of an increase in serum creatinine (> 20% of baseline levels) was 51%. The increase in creatinine was associated with sclerosing arteriopathy as a marker of chronic rejection in 29 of 43 graft biopsies. The addition of azathioprine had no effect on the stability of long-term graft function and did not influence the 7-year graft survival rate in this highly selected group of patients.

Interstitial nephritis with reversible renal failure due to a copper-containing intrauterine contraceptive device.

A 41-year-old woman was admitted to the hospital because of renal failure requiring hemodialysis treatment. Renal biopsy revealed active chronic interstitial nephritis. Renal function nearly normalized after removal of a copper-containing intrauterine device (IUCD). We conclude that copper-IUCDs may lead to renal failure in women with copper allergy.

Recurrent and de novo renal disease after kidney transplantation with or without cyclosporine A.

We evaluated the clinical course of 700 renal transplantations, including 1,305 transplant histologies performed in 611 patients between 1970 and 1988, to estimate the influence of cyclosporine A (CsA) after kidney transplantation on the incidence of recurrent or de novo renal disease. Primary renal disease recurred in 11 of 583 functioning transplants (1.9%) with transplant loss in seven patients (1.2%): focal segmental glomerulosclerosis (FSGS, three patients); membranous glomerulonephritis (GN, one patient); mesangiocapillary GN (one patient); rapidly progressive IgA nephropathy (one patient); hemolytic-uremic syndrome (HUS, three patients); and oxalosis in two transplants (one patient). De novo renal disease occurred in six patients (1.0%), including mesangiocapillary GN type I (three patients); nonpurulent focal GN in septicemia (one patient); HUS (one patient); and nodular glomerulosclerosis in steroid diabetes (one patient). De novo membranous GN was seen in 14 additional cases (2.4%). No statistically significant difference could be established between the treatment groups without (n = 225) and with (n = 358) CsA in recurrent and de novo renal disease (n = 7/225 v 10/358, NS); in recurrent and de novo GN (n = 4/225 v 6/358, NS); in recurrent FSGS (n = 1/7 v 2/8, NS); in recurrent and de novo HUS (n - 1/1 v 2/7, NS); and in de novo membranous GN (n = 7/225 v 7/358, NS). Transplant loss by recurrent and de novo GN was higher without than with CsA (n = 4/4 v 1/6, P = 0.004). On the basis of our investigation, we conclude that recurrent and de novo renal disease in the transplant occur rarely and are not prevented by CsA. However, even if the incidence of transplant GN is unchanged by CsA treatment, its clinical course seems to be mitigated. CsA treatment also does not increase the incidence of HUS.

Hepatic involvement in patients with human immunodeficiency virus infection: discrepancies between AIDS patients and those with earlier stages of infection.

The effect of human immunodeficiency virus (HIV) infection on type and severity of liver disease was studied in 61 HIV-positive patients who did not have AIDS and in 45 AIDS patients. Liver biopsies revealed viral hepatitis in 12 of 18 non-AIDS patients but in only 4 of 34 AIDS patients (P less than .0005, Fisher's exact test). Acute, non-A non-B, and chronic active hepatitis B were seen exclusively in the non-AIDS group; however, chronic persistent hepatitis B was seen in both groups. In 9 of 18 AIDS patients intra vitam liver histopathology established diagnoses of opportunistic infections or tumors. Tissue reaction to certain pathogens, such as hepatitis B virus, mycobacteria, and cryptococci, seems to be milder in AIDS patients than in others who are HIV positive or the expected reaction of the normal host. This is likely because of impaired cell-mediated immunity in patients with advanced HIV disease.

[Microscopic DNA cytophotometry of axillary lymph node metastasis in mammary carcinomas]. / Mikroskopische DNS-Zytophotometrie axillärer Lymphknoten-Metastasen beim Mamma-Carcinom.

65 primary mammary carcinomas and their corresponding axillary lymphnode metastases were studied. DNA-histograms were measured in imprints using microscopical Feulgen-cytophotometry (CAS 100). Comparison between DNA histograms according to AUER-typing showed a close consent in all except five cases; with a shifting from euploidy to aneuploidy (one case), and from aneuploidy to euploidy (four cases). The clinical value of these findings should be proved.

Late conversion from steroids to azathioprine in cyclosporin-treated renal graft recipients.

In renal graft recipients primarily treated with cyclosporin and low-dose methylprednisolone, withdrawal of the long-term steroid medication increases the likelihood of developing rejection episodes. In order to determine the predictive value of clinical parameters and routine prewithdrawal graft biopsies for the risk of rejection, the authors studied 141 kidney recipients from whom steroids were withdrawn 7-9 months after transplantation in a clinically stable situation. Both the quality of the HLA-match and the results of prospective graft biopsies were found to correlate significantly to the occurrence of acute rejection. In order to investigate the influence of additional azathioprine medication on the incidence of acute rejections in recipients not receiving steroids, immunosuppression was continued with cyclosporin monotherapy in 88 patients and with cyclosporin plus azathioprine in 53 patients. The risk of developing rejection episodes was significantly reduced from 48% after 1 year on monotherapy to 28% after the addition of azathioprine medication.

Granulomatous interstitial nephritis after nonsteroidal anti-inflammatory drugs.

Electrolyte and renal hemodynamic imbalance, acute interstitial nephritis with nephrotic-range proteinuria, papillary necrosis, tubular necrosis, and vasculitis are complications after intake of nonsteroidal anti-inflammatory drugs (NSAID). We report on 2 cases of biopsy-proven granulomatous interstitial nephritis with rapidly progressing renal insufficiency. Patient 1 was on ketoprofen for 7 months and indomethacin for 10 weeks before admission to hospital. The medication was not discontinued and renal insufficiency progressed to end-stage renal failure. Renal function did not respond to steroid and tuberculostatic treatment. Patient 2 was on diclofenac for 6 months and indomethacin for 7 weeks before admission to hospital. These drugs were withdrawn at diagnosis and renal function rapidly improved. We conclude that granulomatous interstitial nephritis may be a complication of NSAID medication indicating a cell-mediated immunologic disorder. False diagnosis (sarcoidosis, tuberculosis) may lead to end-stage renal disease (case 1). Discontinuation of medication obviates further therapy (case 2).

Acute interstitial nephritis and non-oliguric renal failure after cefaclor treatment.

A case of acute interstitial nephritis (AIN) developing after cefaclor treatment is reported. Diagnosis was proofed by kidney biopsy and lymphocyte transformation test. The clinical course of the patient with non-oliguric renal failure was favourable. Four weeks after discontinuation of cefaclor treatment the renal function was completely restored and remained stable over the ten-month follow-up period. It is concluded that cefaclor can cause hyperallergic AIN and acute renal failure.

Haemodialysis in 'hepatorenal syndrome': report on two cases.

We report two patients with hepatorenal syndrome who recovered from oliguria and renal failure after temporary treatment with haemodialysis. Hepatorenal syndrome developed under diuretic treatment in both patients. Volume expansion, dopamine, and prostaglandin I2 did not improve renal function. In the one patient with alcoholic cirrhosis, renal biopsy showed only minimal alterations of glomeruli, tubuli, and arterial vessels. In the other case, the deterioration and improvement in renal function parallelled changes in acute alcohol-toxic hepatic function. We conclude that haemodialysis should be considered for treatment of hepatorenal syndrome in selected patients where reversal of liver failure can be expected.

[Acute kidney failure in secondary renal oxalosis. Additional indications for a causal connection to xylitol infusions]. / Akutes Nierenversagen bei sekundärer renaler Oxalose. Weitere Hinweise auf ursächlichen Zusammenhang mit Xylitinfusion.

A 35 years old female developed a slowly progressive acute renal failure after surgical drainage of a pancreatic abscess. Due to the uncharacteristic course a renal biopsy was performed which revealed a severe obstructive renal oxalosis with concomitant interstitial nephritis. Primary oxalosis was excluded by determination of glyceric and glycolic acid in the urine. Since other preconditions for increased oxalate formation were not present it was considered as an adverse reaction to the parenteral application of xylitol. During 4 weeks of total parenteral nutrition the patient received this sugar alcohol in a dose of 3.0 g/kg/day (total dose 4480 g). In recognition of preceding autopsy studies and recent experimental investigations on the metabolic pathways from xylitol to oxalate the chances and conditions of renal deposition of calcium oxalate after administration of xylitol are discussed.

[Acute interstitial nephritis caused by drugs]. / Akute interstitielle Nephritis durch Medikamente.

Within 30 months the diagnosis of drug-induced acute interstitial nephritis was made in ten patients with acute onset of renal failure of clinically unknown cause. Allergenic substances were discovered to be antibiotics, pyrazol and indol derivatives, piromidic acid and chlorazanil. In contrast to the known course of methicillin nephritis the clinical signs were undramatic. Non-oliguric renal failure predominated, sometimes with leucocyturia, microhaematuria and moderate proteinuria. Intermittent haemodialysis was necessary in half the cases. Renal function developed favourably without further specific treatment, however, plasma creatinine did not return to normal levels in most cases. Percutaneous renal biopsy was the definitive diagnostic step. Indications for biopsy in cases of unclear acute renal failure should thus be handled liberally in order to prevent continued drug exposure with the danger of irreversible renal failure.

De novo membrano-proliferative glomerulonephritis in a renal allograft.

De novo glomerulonephritis (GN) in the graft is an uncommon complication of renal transplantation. We report a case of de novo membrano-proliferative GN which occurred in a second cadaver allograft in a 42-year-old woman, who developed severe hypertension, nephrotic syndrome, and progressive renal failure. Our material and a review of the literature suggest an incidence of de novo GN of about 0.5-2%. In contrast to most of the cases described by other authors, the membrano-proliferative type of de novo GN in renal allografts seems to be very rare.

The significance of chromosomal findings for the differentiation between lymphoma and lymphoblastoid cell lines.

Cytogenetic studies have been performed from four Burkitt's lymphoma cell lines, one cell line obtained after successful xenotransplantation of a Burkitt's lymphoma cell line into athymic nude mice, and from ten lymphoblastoid cell lines (three derived from umbilical cord blood cells, one from acute myelogenous leukemia and six from Hodgkin's disease specimens). Our findings indicate the non-neoplastic nature of lymphoblastoid cell lines in spite of their high proliferative activity in vitro and their aneuploidy after long-term cultivation. In contrast, cell lines of Burkitt's lymphoma origin apparently are truly malignant lymphoma cells, characterized by aneuploidy and by the presence of a 14q+-marker chromosome even in the EBV-negative cell lines. The 14q+-marker chromosome, observed in Burkitt's lymphoma as well as in other malignant lymphomas, seems to be related to neoplasia, independent on the presence of EBV. The significance of the aneuploidy for the differentiation between lymphoma and lymphoblastoid cell lines is discussed.

[Rapidly progressive glomerulonephritis in a child. Clinical and histological observation over 3 1/2 years (author's transl)]. / Perakute Glomerulonephritis beim Kind. Klinische und bioptische Verlaufsbeobachtung über 3 1/2 Jahre

At the age of 5 years and 10 months a boy suffered from rapidly progressive glomerulonephritis. After 14 days of treatment with peritoneal dialysis and chlorambucil the acute renal failure was overcome and the kidneys started to function again. 3 1/2 years later 2/3 of normal values for glomerular filtration had been regained, though proteinuria is still 2,8 g/day. Histologically mainly extracapillary proliferations and a partially necrotizing glomerulonephritis were seen in the beginning. 1 1/4 years later sklerosed glomerula predominated (80%) over almost normal glomerula with only minor proliferations. The prognosis remains doubtful in spite of the benign course in the beginning.