Nocardia Infection in Nephrotic Syndrome Patients: Three Case Studies and A Systematic Literature Review.

OBJECTIVE: The multicenter literature review and case studies of 3 patients were undertaken to provide an updated understanding of nocardiosis, an opportunistic bacterial infection affecting immunosuppressed nephrotic syndrome (NS) patients receiving long-term glucocorticoid and immunosuppressant treatment. The results provided clinical and microbiological data to assist physicians in managing nocardiosis patients. METHODS: Three cases between 2017 and 2018 from a single center were reported. Additionally, a systematic review of multicenter cases described in the NCBI PubMed, Web of Science, and Embase in English between January 1, 2001 and May 10, 2021 was conducted. RESULTS: This study described three cases of Nocardia infection in NS patients. The systematic literature review identified 24 cases with sufficient individual patient data. A total of 27 cases extracted from the literature review showed that most patients were > 50 years of age and 70.4% were male. Furthermore, the glucocorticoid or corticosteroid mean dose was 30.9 ± 13.7 mg per day. The average time between hormone therapy and Nocardia infection was 8.5 ± 9.7 months. Pulmonary (85.2%) and skin (44.4%) infections were the most common manifestations in NS patients, with disseminated infections in 77.8% of patients. Nodule/masses and consolidations were the major radiological manifestations. Most patients showed elevated inflammatory biomarkers levels, including white blood cell counts, neutrophils percentage, and C-reactive protein. Twenty-five patients received trimethoprim-sulfamethoxazole monotherapy (18.5%) or trimethoprim-sulfamethoxazole-based multidrug therapy (74.1%), and the remaining two patients (7.4%) received biapenem monotherapy. All patients, except the two who were lost to follow-up, survived without relapse after antibiotic therapy. CONCLUSIONS: Nephrotic syndrome patients are at high risk of Nocardia infection even if receiving low-dose glucocorticoid during the maintenance therapy. The most common manifestations of nocardiosis in NS patients include abnormal lungs revealing nodules and consolidations, skin and subcutaneous abscesses. The NS patients have a high rate of disseminated and cutaneous infections but a low mortality rate. Accurate and prompt microbiological diagnosis is critical for early treatment, besides the combination of appropriate antibiotic therapy and surgical drainage when needed for an improved prognosis.

Renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in Europe.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae The main clinical manifestations involve the skin and the peripheral nervous system. Several types of nephropathy have been described in leprosy. One frequent form of renal involvement is amyloidosis, especially in patients with lepromatous leprosy. In these patients, end-stage renal disease is an important contributor to morbidity and mortality. Here, we present the case of a patient with nephrotic syndrome caused by secondary amyloidosis, chronic peripheral neuropathy and a history of leprosy. The patient was correctly treated in her youth, which is the best way to avoid renal pathology, but she developed a nephrotic syndrome years later.

Renal involvement in leprosy.

Renal involvement in Hansen's disease was evaluated in 94 Portuguese patients, average age and duration of disease of 47.6 and 6.8 years respectively. Sixty-seven were studied retrospectively and 27 prospectively; renal biopsy was obtained in 4, fat-tissue needle aspiration for amyloidosis in 20, and tubular function was tested in ten. Mild proteinuria and/or haematuria was found in 33 patients, the severity increasing during erythema nodosum leprosum reactions, but without overt nephritic or nephrotic syndrome. Two patients had renal amyloidosis on biopsy and two more were confirmed by fat biopsy, a 10.5% incidence in those studied prospectively; all but one were of the lepromatous type, with frequent bouts of erythema nodosum leprosum. The two other renal biopsies showed mesangial glomerulonephritis, and one unexplained acute tubular necrosis; none had immune deposits by immunofluorescence. Proximal acidification was always normal, distal acidification tested by bicarbonate infusion was abnormal in one of nine patients, and six of nine patients had concentration defects. Leprosy causes frequent urinary sediment changes and concentration defects, usually without clinical expression; proteinuria and/or glomerular involvement is mainly due to amyloidosis.

Renal disease in adult Indians: a clinicopathological study of 2,827 patients.

Nephrotic syndrome was the commonest clinical presentation among 2827 consecutive adult Indian patients from whom adequate kidney biopsies were obtained for suspected renal disease. In 83 per cent of cases the nephrotic syndrome was due to minimal change disease, focal segmental glomerulosclerosis, mesangiocapillary glomerulonephritis, membranous usually secondary to tuberculosis or leprosy, was present in only 34 patients. Acute nephritis, the next most frequent clinical presentation, was due to diffuse endocapillary proliferative, crescentic or mesangial proliferative glomerulonephritis in 88 per cent of cases, almost half of whom had elevated serum streptococcal antibody titres. Eosinophilia showed a highly significant association with diffuse endocapillary proliferative and mesangiocapillary glomerulonephritis. Idiopathic IgA nephropathy was present in only 10, and antiglomerular basement membrane antibody disease in only one, of the 238 patients whose biopsies were studied by immunofluorescence. Complications of pregnancy accounted for 70 per cent of cases of cortical necrosis. Acute gastroenteritis, septicaemia, abortions, snake bite and allopathic and indigenous medicines were important causes of acute tubular necrosis.

The role of infectious agents in the aetiology and pathogenesis of childhood nephrotic syndrome in Africa.

Childhood nephrotic syndrome is common in Africa where infectious agents are prevalent. This paper reviews the possible aetiological role of infectious agents in childhood nephrotic syndrome in Africa. There is a strong association, possibly causal, between childhood nephrotic syndrome on the one hand and Plasmodium malariae, Schistosoma mansoni and hepatitis B antigens on the other. Beta-haemolytic streptococci are less strongly associated with nephrotic syndrome, and a few other organisms are suspect. The many ubiquitous infectious agents and the prevalence of multiple infections make it difficult to define the role of any single infectious agent or to determine the interaction between the various agents. Control or eradication of infectious diseases should lower the incidence of childhood nephrotic syndrome in Africa.

Immunologic aspects of leprosy with reference to extravascular immunoglobulins: their excretion profile in urine.

An aliquot of 24-hour urine collected from leprosy patients was concentrated and examined for the presence of albumin, transferrin, IgG, IgA, IgM, IgD, D3, kappa and lambda light chains by the gel diffusion technic using respective monospecific antisera. Urinary protein excretion profile in lepromatous leprosy patients showed that while excretion of transferrin in the urine was negligible; that of IgG molecules, a substance of higher molecular weight, was significant. It is suggested that the immunoglobulins excreted in the urine may not be plasma-derived, but extravascular in origin. They are probably synthesized in the urinary tract. In the present study, out of 25 leprosy patients, 2 female patients having severe lepra reactions developed urinary tract infections. E. coli and Klebsiella were isolated from their urine. The urinary IgG levels in those two cases were found to be the highest in the series.