Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha.

INTRODUCTION: Chronic kidney disease (CKD) is emerging as a serious health problem in Odisha, India. A new form of severe CKD affecting adults, not due to traditional risk factors like diabetes, hypertension, glomerulonephritis, has been reported in Sri Lanka, Central America, and Egypt in the last two decades. This has been named CKD of unknown origin (CKDu), and it is fatal due to late recognition and rapid disease progression. The aim of the study was to elucidate the association between different sociodemographic, and biochemical parameters with renal morphology in CKD of unknown origin patients. METHODS: A cross-sectional study was conducted on 124 consecutive patients with CKD from the period January 2018 to December 2018. Patients in the age group 18-60 years who met clinical criteria for CKD were included. Participants answered a questionnaire. After the necessary history, clinical evaluation, and blood and urine analyses, a kidney biopsy was undertaken. Kidney biopsy was feasible in 51 patients as the rest 61 patients had shrunken kidneys and 12 patients did not give consent. Patients with diabetes mellitus (DM), hypertension, glomerulonephritis, polycystic kidney disease, obstructive kidney disease or any other congenital diseases, snakebite, pregnancy, malignancy, gout, primary hyperparathyroidism, infectious diseases like human immunodeficiency virus (HIV), TB, Hepatitis B and C, malaria, syphilis, leprosy and coagulopathies were excluded. Among the 51 patients, 23 had CKDu, 25 had chronic glomerulonephritis and three biopsies were inconclusive. RESULTS: The mean age of CKDu patients was 36.78 ± 9.85 years. Males (73.9%) were predominantly affected. A family history of CKD was seen in 82.6% of CKDu cases. Hyponatremia and hypokalemia were predominant biochemical abnormalities in our CKDu cases. Binary logistic regression showed rural residence, family history of CKD, exposure to smoke from burning coal, charcoal, or biomass fuels, low socioeconomic status, and low body mass index were strongly associated with CKDu. There was an increased risk of developing CKDu in persons with a family history of CKD [p = 0.003, odds ratio (OR)- 17.58], persons exposed to smoke from burning coal, charcoal or biomass fuels (p = 0.003, OR- 32.4), and patients with low socio-economic status (p = 0.001, OR- 15.87). Interstitial fibrosis (IF), interstitial inflammation with mononuclear infiltration, tubular atrophy (TA), and global glomerulosclerosis (GS) were pertinent histopathological findings in our study. CONCLUSION: There is no strong evidence for a single cause for CKDu, and multiple environmental, occupational and social factors are probably involved. We need to design consistent and comparative multisite studies to identify etiologies of CKDu, across high-risk populations that may help elucidate the importance of region-specific vs global risk factors.

Dive deep into trophic ulcer; Glomerulonephritis is still a complication in hansen's disease.

Hansen's disease is one of the ancient skin diseases known to humankind, still foxes even trained physician leading to delay in its diagnosis and unusual health burden. India followed by Brazil constitutes the highest number in newly diagnosed cases. Even though the World Health Organization and individual country have done much to contain the spread of leprosy, the findings of systemic complications, grade 2 deformity, and childhood leprosy reflect some shortcomings of the worldwide public health program. Renal involvement, particularly glomerulonephritis, is a known common systemic complication of the leprosy, but introduction of multidrug therapy and early case detection have reduced the chances of systemic complication significantly over the last three decades. Here, we report a case who presented in the emergency department with rapidly progressive swelling of the body, on evaluation found to have leprosy and glomerulonephritis having tubuloreticular inclusions in glomerular endothelial cell cytoplasm on electron microscopy.

Hansen's disease with lepra reaction presenting with IgA dominant infection related glomerulonephritis.

Various renal abnormalities in leprosy have been described largely in literature but the occurrence of IgA dominant infection related glomerulonephritis in leprosy with type 2 lepra reaction has not been reported so far. We present here a 60-year-old man with a history of leprosy in the past admitted with type 2 lepra reaction, rapidly progressive glomerulonephritis with severe renal failure requiring dialysis and diagnosed to have IgA dominant infection related glomerulonephritis.

Glomerulonefritis por inmunocomplejos en un paciente con lepra / Immune-complex glomerulonephritis in a patient with leprosy

La lepra es una enfermedad cuyas manifestaciones se dan a nivel cutáneo y neurológico periférico. Es conocida desde siglos atrás y continúa siendo un problema de salud pública a nivel mundial. La prevalencia ha disminuido después de la instauración de esquemas de tratamiento poliquimioterápicos. En Colombia no está considerada como un problema de salud pública por su baja prevalencia. El compromiso multisistémico es común, especialmente en las formas multibacilares. Los sistemas articular y renal son frecuentemente afectados, aunque estas afectaciones son en muchas ocasiones pasadas por alto. Se reporta el caso de un paciente con lepra lepromatosa que presentó glomerulonefritis mediada por inmunocomplejos y, además, compromiso poliarticular secundario a una reacción leprosa del tipo eritema nudoso lepromatoso. No hay conciencia por parte del personal de salud sobre las características de la enfermedad, ya que en muchos casos se cree erradicada. Este caso ilustra la importancia del reconocimiento y tratamiento oportunos para prevenir la discapacidad asociada.

Leprosy is a disease whose manifestations are seen in the skin and at the peripheral neurological level. It has been known for centuries and remains a public health problem worldwide; however its prevalence has declined after the introduction of multidrug treatment schemes. In Colombia leprosy is not considered a public health problem because of its low incidence. Multisystem compromise is common, especially in multibacillary forms, with the articular and renal systems commonly affected; although these effects are often overlooked. We report a patient with lepromatous leprosy who presented immune-mediated glomerulonephritis and polyarticular impairment secondary to erythaema nodosum leprosum. There is no awareness on the part of health personnel on the characteristics of the disease and in many cases are believed eradicated. This case illustrates the importance of early recognition and timely treatment to prevent disability associated.

Glomerulonefritis extracapilar y lepra: una asociación infrecuente / Extracapillary glomerulonephritis and leprosy: An uncommon association

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The involvement of upper airway in Wegener's granulomatosis - about four cases.

The authors present four cases of Wegener's granulomatosis patients with multiorganic manifestation forms, but with a prevalent involvement in upper-airway. Granulomatosis diseases of the nose include bacterial infections (rhinoscleroma, tuberculosis, syphilis, lupus, and leprosy), fungal infections (rhinosporidiosis, aspergillosis, mucormycosis, candidosis, histoplasmosis, and blastomycosis) and diseases with unspecified etiology (Wegener's granulomatosis, mediofacial malignant granuloma, and sarcoidosis). We consider an interesting experience regarding Wegener's granulomatosis due to its rarity, being an autoimmune systemic disease, with continuous evolution and multiorganic involvement. The beginning of the disease is like upper airway affection, a kind of "persistent cold", being difficult to differentiate it from a common cold in the head, with a prolonged evolution. It is important to mention that we establish the diagnosis of Wegener's granulomatosis starting with Ear Nose and Throat (ENT) clinical exam, followed by other tests and investigations realized in our Clinic and completed with specialty tests (nephrology, internal medicine and dermatology), meaning that we need a close cooperation with these medical specialties. All the patients presented multiorganic involvement. Notably significant for our four cases is the prolonged evolution in a stable condition in one patient.

It is time to review concepts on renal involvement in leprosy: pre- and post-treatment evaluation of 189 patients.

BACKGROUND: Functional and morphological renal lesions have been widely described in leprosy for decades. Nevertheless few studies have assessed renal function pre- and during treatment after the advent of multidrug therapy (MDT). METHODS: This is a prospective study involving 189 consecutive patients, with all forms of leprosy (Ridley-Jopling scale). Laboratory (serum urea and creatinine, estimated GFR, urinalysis, microalbuminuria, urinary RBP) and clinical features of renal disease were evaluated previously and after onset (3 and 8 months later) of MDT. RESULTS: One hundred and eighty-nine patients (M 1.8: F 1; mean age 44 ± 16 years) were included just after diagnosis of leprosy and before the introduction of MDT. Mean time until manifestation of symptoms and/or signs of leprosy was 29 ± 56 months (25 days-480 months). Microhematuria and microalbuminuria were detected in 7.5% and 9.6% of the cases, respectively. Elevated serum creatinine was detected in 34% pre-MDT; this was statistically more frequent in males, hypertensive and frequent users of non-steroidal anti-inflammatory drugs (NSAID), as well as in patients with erythema nodosum lepromatosum, 45.5% by the time of diagnosis, 18% after 3 months and 9% after 8 months of MDT (p = 0.039). CONCLUSIONS: Our results suggest that functional renal lesions in leprosy are currently mild and predominantly of glomerular origin, in opposition to the severe involvement described in the past. This improved outcome of renal disease secondary to leprosy is possibly due to the advent of MDT and effective treatment of episodes of reaction, leading to shorter periods of active infectious disease.

Crescentic glomerulonephritis: a clinical and histomorphological analysis of 46 cases.

BACKGROUND: Crescentic glomerulonephritis (CrGN), defined as crescents involving more than 50% of the glomeruli, includes pauci-immune, immune complex-mediated and anti-glomerular basement membrane disease. OBJECTIVES: The present study was aimed at evaluating the various clinical, biochemical and histological parameters in CrGN with respect to these categories and clinical outcome. MATERIALS AND METHODS: Renal biopsies diagnosed as CrGN between Jan 2008 and Feb 2010 were included. Clinical and laboratory parameters were retrieved along with the therapeutic approach and clinical outcome, wherever available. Renal biopsy slides were evaluated for various glomerular, tubulo-interstitial and arteriolar features. Appropriate statistical tests were applied for significance. RESULTS: A total of 46 cases of CrGN were included; majority (71.7%) of cases were pauci-immune (PI) while 28.3% were immune complex-mediated (IC). Among clinical features, gender ratio was significantly different between PI and IC groups (P = 0.006). The various histological parameters, including proportion of cellular crescents, tuft necrosis and Bowman's capsule rupture, were similar in both the groups. Four unusual associations, including idiopathic membranoproliferative glomerulonephritis (MPGN), multibacillary leprosy, acute lymphoblastic leukemia and C1q nephropathy were detected. Adequate follow-up information was available in 21 (46%) of the patients. Of these, 11 (52.4%) were dialysis-dependent at the last follow-up. Adult patients required renal replacement therapy more frequently than pediatric cases (P = 0.05). Presence of arteriolar fibrinoid necrosis also showed association with poor clinical outcome (P = 0.05). CONCLUSIONS: Crescentic glomerulonephritis remains one of the main causes of acute renal failure with histological diagnosis. Immunohistologic examination is essential for accurate classification into one of the three categories. This condition should be considered in rare causal associations like leprosy or MPGN with renal failure, to allow for timely performed renal biopsy and appropriate aggressive therapy.

Acute glomerulonephritis in a child with multidrug-resistant tuberculosis and multibacillary leprosy.

A 10-year-old boy from Papua New Guinea with multidrug-resistant tuberculosis and multibacillary leprosy developed acute glomerulonephritis while being treated as an inpatient at Thursday Island Hospital in the Torres Strait, Queensland. This is the first such case to be reported in Australia, where these diseases are uncommon and the combination is extremely rare, and it outlines important learning points regarding the aetiology of renal disease among patients with tuberculosis and leprosy.

Renal involvement in leprosy: report of progression from diffuse proliferative to crescentic glomerulonephritis.

Renal involvement in leprosy has been reported rarely in the literature. Acute kidney injury in patients with leprosy is uncommon and may occur due to acute tubular necrosis, drug-induced interstitial nephritis and rarely crescentic glomerulonephritis. The latter with histologic confirmation of the diagnosis has been reported in very few cases of leprosy. A 25-year-old male, on therapy for multibacillary leprosy, was found to have deranged renal functions on evaluation for a history of nausea, vomiting, swelling and episode of haematuria. Kidney biopsy was performed twice over a period of 2 weeks, showing progression from diffuse proliferative glomerulonephritis to crescentic glomerulonephritis, pauci-immune in nature. The patient was treated aggressively with intravenous steroids, following which his renal functions stabilized. Crescentic glomerulonephritis, an extremely rare phenomenon in leprosy, should be considered in these patients presenting with features of acute kidney injury. Timely performed renal biopsy assists in accurate diagnosis and appropriate management of the patient, hence preserving renal parenchyma. Rapid progression from diffuse proliferative glomerulonephritis to crescentic glomerulonephritis in a patient with leprosy is described herein for the first time in the literature.

Administration of M. leprae Hsp65 interferes with the murine lupus progression.

The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K(409)A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F(1) mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F(1) serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K(409)A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K(409)A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process.

[The sequelae of Hansen's disease. (Pathologic viewpoint of etiologies, morphologies and countermeasures)].

The proportion of glomerulonephritis, often a sequence of arteriolitis, among the sequelae of Hansen's disease after the introduction of chemotherapy increased markedly in Japan and nullified that of once prevalent tuberculosis after 1960s. However, most significant aftermath of the disease for numbers of years in the past have been peripheral nerve injuries worldwide for which effective countermeasures are yet to be developed. In this brief autopsy cases study from 1960s to 1990s, we confirmed the presence of cases in which arteriolitis and resulted infarction of peripheral nerves and not M. leprae itself were shown to be the major cause of axonal damages. There were also cases in which the accumulation of the bacilli without vascular changes did not damage the axons. The cases as these could not be solitary but should be rather common in this time of chemotherapy. If so, the methods to reconstruct nerves and blood vessels by promoting those regeneration should be developed to cope with the situation for surgeon, assisted by pathologists.

Glomerular disease in the tropics.

Glomerular disease in the tropics differs considerably from that in temperate climates and between the developed and the developing world. The prevalence and pattern of glomerular disease in the tropics in turn varies widely in different geographic regions and is influenced by environmental, nutritional, and socioeconomic factors. Among the infective agents that have been identified as contributing to an increased prevalence of glomerular disease in the tropics are Plasmodium malaria, Schistsomiasis mansoni, Mycobacterium leprosy, and hepatitis B virus (HBV). A decline in the prevalence can only be expected with the eradication of infections. Accurate knowledge of the prevalence, histologic features, and causes is essential to achieve prevention and management of glomerular diseases in the tropics.

Glomerular disease in the tropics

Glomerular disease in the tropics differs considerably from that in temperate climates and between the developed and the developing world. The prevalence and pattern of glomerular disease in the tropics in turn varies widely in different geographic regions and is influenced by environmental, nutritional, and socioeconomic factors. Among the infective agents that have been identified as contributing to an increased prevalence of glomerular disease in the tropics are Plasmodium malaria, Schistsomiasis mansoni, Mycobacterium leprosy, and hepatitis B virus (HBV). A decline in the prevalence can only be expected with the eradication of infections. Accurate knowledge of the prevalence, histologic features, and causes is essential to achieve prevention and management of glomerular diseases in the tropics.

La lepra y el riñon / Leprosy and the kidneys

Revisamos los efectos causados por la lepra sobre riñón, los cuales no se deben a la presencia del bacilo en los nervios o en parenquima renal, sino fenómenos secundarios, tales como formación de complejos inmunes, precipitación de proteínas resultantes de la inflamación crónica o complicaciones de la terapia antileprosa, principalmente. Se incluye: a) defectos en la concentración y acidificación de la orina, b) nefritis intersticial aguda o crónica, c) insuficiencia renal aguda, d) amiloidosis sistémica secundaria, e) glomerulonefritis. Se analizan los mecanismos por los cuales se producen estas lesiones y se describen las circunstancias documentadas sobre la lepra y transplante renal. La lepra no es una contraindicación para este transplante porque si bien se requiere de inmunosupresión, la enfermedad puede no reactivarse y si lo hace, se controla con la poliquimioterapia disponible. La lesión renal en la lepra predomina en los enfermos multibacilares y en la reacciones de tipo 2 o eritema nodoso leproso. En general es silenciosa, crónica y puede llegar a ser causa de muerte en estos enfermos. Se detecta con facilidad con el simple examen parcial de orina, que revela albuminuria, cilindruria y hematuria. Este examen debe hacerse en todo paciente con lepra y debe tener carácter obligatorio en la reacción tipo 2, en la cual, junto con los síntomas cutáneos, neuríticos y oculares, se presenta algún grado de compromiso renal, en el 100 por ciento de las reacciones. El compromiso renal que la lepra produce en los enfermos colombianos, se ha relegado a un segundo plano ante las manifestaciones dermatológicas. Se ha documentado amiloidosis secundaria sistémica y glomerulonefritis por depósito de complejos inmunes

Crescentic glomerulonephritis due to rifampin treatment in a patient with pulmonary atypical mycobacteriosis.

A 64-year-old male was treated continuously with rifampin, isoniazid and streptomycin for pulmonary atypical mycobacteriosis, Mycobacterium kansasii. Five weeks after beginning the treatment, the patient suddenly developed acute renal failure. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis with moderate interstitial changes. Serum antirifampin antibody was detected, and the cessation of rifampin treatment was followed by a rapid spontaneous recovery of the patient's renal function. This is, to our knowledge, the first case of rapidly progressive crescentic glomerulonephritis associated with rifampin treatment where circulating antirifampin antibody is demonstrated and the renal function spontaneously improved after discontinuing rifampin treatment.