[Renal Side Effects of Novel Molecular Targeted Oncologic Agents].

The introduction of innovative therapies has changed the scenario of complications. The delay in the recognition of kidney adverse effects is partly due to the timing of the development of the kidney damage which occurs later than the observation period of registration studies, and partly to the exclusion of patients with known kidney impairment from registration trials. Renal disease has a significant impact on the management of cancer patients and often leads to discontinuation of therapy. Histological evaluations of kidney disorders induced by targeted/immunotherapy are very limited. Renal biopsy is critical for the management of renal toxicities and should be especially encouraged for patients showing adverse renal effects to novel cancer agents. We recently examined the histological features of patients treated with new cancer agents who underwent renal biopsy for new onset renal failure and/or urinary abnormalities. The cohort included 42 patients. The most frequently administered therapies were immunotherapy (54.8%) and anti-angiogenic treatments (45.2%). The most common adverse effect was tubular interstitial nephritis in the first group and thrombotic microangiopathy in the second one. Based on histological findings, definitive discontinuation of treatment could be restricted to a very limited number of patients. All of them had anti-VEGF-related TMA. Treatment discontinuation was unneeded in patients treated with ICIs. In patients treated with multidrug therapy, the histological findings made it possible to identify the weight of drug-related specific injury. Based on this data, renal biopsy should be considered in every cancer patient who develops urinary abnormalities or shows a worsening of renal function during treatment with immunotherapy or targeted therapy.

Kidney biomarkers in tropical infections: an update.

Neglected tropical diseases affect over 1 billion people, and cause 170,000 deaths each year. They result in disability, stigma and disfigurement, and also push families into poverty. Tropical infections can involve the kidney, presenting as a wide variety of ways, varying from transient urinary abnormalities to severe acute kidney injury (AKI). It is important to assess renal function in patients with tropical infections for earlier detection of AKI, appropriate treatment and prevention of Chronic Kidney Disease (CKD) outcome in some of them. There was an exponential increase in research on new kidney biomarkers that were earlier and specific for renal damage but few in the scope of tropical infections. In this review, we focus on kidney biomarkers that are being studied in some of the most prevalent tropical infections such as visceral leishmaniasis, leptospirosis, malaria, schistosomiasis and leprosy. Further studies are needed to evaluate the usefulness of renal biomarkers in the early diagnosis of renal diseases associated with tropical infections.

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.

Acute renal failure by rapidly progressive glomerulonephritis with IgA deposition in a patient concomitantly diagnosed with multibacillary Hansen's disease: a case report.

Rapidly progressive glomerulonephritis (RPGN) is a renal disease with an extensive differential diagnosis. This paper reports the case of a 55-year-old female patient diagnosed with Hansen's disease with acute progressive renal impairment after developing lower limb pyoderma. The association between Hansen's and kidney disease has been well documented, with glomerulonephritis (GN) ranked as the most common form of renal involvement. Post-infectious glomerulonephritis (PIGN) in adults has been associated with a number of pathogens occurring in diverse sites. The patient described in this case report had RPGN and biopsy findings suggestive of PIGN with C3 and IgA detected on immunofluorescence and kidney injury secondary to recent infection by Staphylococcus, a well-documented manifestation of renal impairment in patients with Hansen's disease.

Urinary monocyte chemotactic protein-1 (MCP-1) in leprosy patients: increased risk for kidney damage.

BACKGROUND: We aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease. METHODS: This is a cross-sectional study of 44 patients with diagnosis of leprosy and no previous treatment. Skin smear was assessed through a bacteriological index - from 0 to 6+. Glomerular filtration rate (GFR), protein excretion rate, microalbuminuria, urinary oxidative stress, malondialdehyde (MDA) and urinary MCP-1 were measured. Also, high- sensitivity C-reactive protein (hs-CRP) was measured in the blood. Fifteen healthy subjects composed a control group. RESULTS: Age and gender were similar between leprosy patients and control groups. No patient had a GFR < 60 mL/min/1.73 m2 or albumin excretion rate greater than 30 mg/g-Cr. Leprosy patients had higher urinary protein excretion (97.6 ± 69.2 vs. 6.5 ± 4.3 mg/g-Cr, p < 0.001), urinary MCP-1 (101.0 ± 79.8 vs. 34.5 ± 14.9 mg/g-Cr, p = 0.006) and urinary MDA levels (1.77 ± 1.31 vs. 1.27 ± 0.66 mmol/g-Cr, p = 0.0372) than healthy controls. There was a positive correlation between urinary MCP-1 and bacteriological index in skin smears (r = 0.322, p = 0.035), urinary protein excretion (r = 0.547, p < 0.001), albumin excretion rate (r = 0.414, p = 0.006) and urinary MDA (r = 0.453, p = 0.002). After adjusting for hs-CRP, urinary MCP-1 remained correlated with albumin excretion rate (rpartial = 0.483, p = 0.007) and MDA levels (rpartial = 0.555, p = 0.001). CONCLUSION: Leprosy patients with no clinical kidney disease have increased urinary MCP-1 mainly in lepromatous polar form. Inflammatory (MCP-1) and oxidative stress markers suggest leprosy patients are at high risk of developing kidney 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.

Toxicological assessment of Ricinus communis Linn root extracts.

Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000 mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000 mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.

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.

Estado Hístico-Funcional del Riñón en la Lepra / No disponible

Se realizó un estudio descriptivo transversal para determinar el comportamiento del estado histo-funcional de los pacientes afectados de lepra en la ciudad de Camagüey en el período comprendido entre el 1º de enero de 2002 al 21 de diciembre del 2003. El universo de estudio quedó constituido por un total de 51 pacientes portadores de lepra que se controlan bajo tratamietno médico. E grupo de edad más frecuente se encontraba entre 56 y 65 años (41,1%), la lepra dimorfa fue las más representativa (50,9%) se concluyó que la defunción renal se presentó en 7pacientes (13,7%), con afecgación mayor en la lepra lepromatosa. La alteración del sedimento urinario predominanate fue la hemturia microscópica en los enfermos que tenían mayor tiempo de evolución y el patrón histopatológico ás frecuente la glomerulonefritis proliferativa mesangial (AU)

A descriptive, cross-sectional study was carried out to determine the behavior of the histo-functional state of patintes affected by leprosy in Camagüey city form Januari 1st, 2002 to Decembre 3st, 2003. The sutdy universe was composed of 51 patients carriers of leprosy who were under medical treatment. The most frequent age group was among 56 and 65 years (41,1%), dimorphous leprosy was the representative (50,9%); it was concluded that renal dysfunction presented in 7 patientes (13,7%), with major affectation in lepromatous leprosy. The urinary sediment disorder frequently was microscopic hematuria and the histopatholoic pattern most frequent the mesanginal proliferaive glomerulophritis (AU)

Renal lesions in leprosy: a retrospective study of 199 autopsies.

In the present work, 199 patients with leprosy who underwent autopsy between 1970 and 1986 were retrospectively studied to determine the prevalence, types, clinical characteristics, and etiologic factors of renal lesions (RLs) in leprosy. Patients were divided into two groups: 144 patients with RLs (RL+) and 55 patients without RLs (RL-). RLs observed in 72% of the autopsied patients were amyloidosis (AMY) in 61 patients (31%), glomerulonephritis (GN) in 29 patients (14%), nephrosclerosis (NPS) in 22 patients (11%), tubulointerstitial nephritis (TIN) in 18 patients (9%), granuloma in 2 patients (1%), and other lesions in 12 patients (6%). AMY occurred most frequently in patients with lepromatous leprosy (36%; nonlepromatous leprosy, 5%; P < 0.01), recurrent erythema nodosum leprosum (33%; P < 0.02), and trophic ulcers (27%; 0.05 < P < 0.10). Ninety-seven percent of AMY was found in patients with lepromatous leprosy, 88% showed recurrent trophic ulcers, and 76% presented with erythema nodosum leprosum. NPS was found in older patients with arterial hypertension, neoplastic diseases, infectious diseases, and vasculitis associated with GN. Most patients with AMY presented with proteinuria (95%) and renal failure (88%). The most frequent causes of death were renal failure in patients with AMY (57%), infectious diseases in patients with GN (41%) and TIN (45%), and cardiovascular diseases in patients with NPS (41%). No difference in survival rates was observed among RL- patients and those with AMY, GN, NPS, or TIN.

Estudo clínico e anátomo-patológico do comprometimento renal em necrópsias de 199 pacientes portadores de hanseníase / ?

Foram estudados retrospectivamente os dados de 199 pacientes com hanseníase, submetidos a autópsia, realizadas no Instituto Lauro de Souza Lima de Bauru, no período de 1970 a 1986, com objetivo de se determinar a prevalência, o tipo e as características das lesoes renais nesta doença. Os dados foram expressos como frequência (por cento) ou mediana (med) e percentis 25 (P25) e 75 (P75). Os pacientes foram divididos em 2 grupos: 144 pacientes com lesao renal (CLR) e 55 sem lesao renal (SLR). As lesoes renais observadas foram: amiloidose (AMI) em 61 pacientes (30,6 por cento); glomerulonefrites (GN) em 29 (14,5 por cento); nefrosclerose (NEFRO) em 22 (11,1 por cento); nefrite tubulointerstical (NTI) em 18 (9,1 por cento); granuloma em 2 (1,0 por cento) e outras lesoes em 12 (6,0 por cento)

[Hansen's disease and nephropathy as its sequence].

Nephropathy as the sequences of Hansen's disease before and after the introduction of chemotherapy was compared referring to the report by Hayashi in 1943 and the summary of the autopsy reports from 1978 to 1981 at National Hansen's disease hospital Zenseien. Unlike the high rates of tuberculosis as the cause of death before the introduction of chemotherapy (41.3%) those thereafter decreased to be negligible. On the other hand the comparison of the rates of nephropathy with the same way as that of tuberculosis was impossible since the description about nephropathy by Hayashi was not sufficient to characterize each nephropathy since he included arteriolitis, glomerulonephritis and interstitial nephritis together in the term of nephritis. Death rate due to nephritis among Hansen's disease patients according to Hayashi at that time was 21.2% which was twice as many comparing to that in the other cases. According to the report about the cases of Zenseien those reported to have glomerulonephritis was 37.3% though those were not necessarily listed as the cause of death. Also the nephropathy including fibrinoid angitis with occasional microaneurysmal dilatation of afferent arteries, glomerulitis, sclerosis and stricture of efferent arteries likewise ischemic acute tubular necrosis possibly as the result of these angiopathy seemed to be present. These vascular changes partially resemble to that of microscopic periarteritis nodosa but seems to be common in the smaller arteries. In conclusion, unlike the case of tuberculosis the rate of nephritis including glomerulitis, arteriolitis and interstitial nephritis as Hayashi used as his criteria does not seem to have decreased. Therefore, the critical analysis of the nephropathy especially of that relating to the arteriolitis should be done to obtain the knowledge to suppress its occurrence.

A fatal case of drug-induced multi-organ damage in a patient with Hansen's disease: dapsone syndrome or rifampicin toxicity?

An elderly patient with borderline tuberculoid Hansen's disease (leprosy) developed the diaminodiphenylsulphone syndrome after approximately 8 weeks of multi-drug therapy comprising dapsone and rifampicin. Postmortem histological examination, following autopsy, demonstrated features consistent with drug-induced hepatitis, tubulo-interstitial nephritis and myocarditis. Although these could have been engendered by dapsone toxicity, it was thought that a concommitant adverse reaction to rifampicin, which is known to be hepatotoxic, nephrotoxic and possibly capable of predisposing to the dapsone syndrome, could not be excluded.

Síndrome da sulfona e reaçäo reversa / Sulfone syndrome and reverse reaction

Um homem de 68 anos de idade, cor preta, interna-se por hanseníase multibacilar, nao tratada, apresentando infiltraçao cutânea difusa e nódulos raros de Eritema nodoso hansênico. Na época, (1982) foi tratado com sulfona e talidomida. Um mês e meio após o início do tratamento surge erupçao cutânea eritematosa difusa, acompanhada de febre alta, adenomegalia generalizada e hepatoesplenomegalia. O hemograma demonstrou leucocitose intensa com linfocitose e atipias de linfócitos. Evoluiu com icterícia, desidrataçao, confusao mental, falecendo no 4( dia após instalaçao da erupçao referida. Na necrópsia o substrato do exantema generalizado é um infiltrado linfocitário pleiomórfico em pele, mucosas e vísceras. Este quadro foi interpretado como a "Síndrome da Sulfona", manifestaçao de hipersensibilidade à esta droga e que em muitos aspectos mimetiza ou induz o aparecimento de uma monucleose infecciosa. Há algumas publicaçoes sobre esta síndrome, algumas relatando casos fatais, más nao há descriçao de achados necroscópicos. Ao lado do infiltrado linfocitário atípico observou-se também reaçao granulomatosa tuberculóide generalizada englobando infiltrado de padrao virchoviano com baciloscopia rica. Os autores acreditam que este quadro representaria uma reaçao reversa induzida pela "Síndrome da Sulfona".

Insuficiência renal aguda pelo uso do esquema multidroga na hanseníase / Acute kidney failure between use of the multiple drug teraphy in leprosy

Sete pacientes consecutivos, de um grupo de 283 portadores de Hanseníase em tratamento com esquema terapêutico multidroga (MDT), foram referidos ao Hospital Evangélico de Londrina e ao Hospital Universitário Regional Norte do Paraná, no período de 1989 a Novembro de 1991, devido a insuficiência renal aguda (I.R.A.). Nestes sete pacientes ocorreram oito episódios de IRA, acompanhados de epigastralgia (8/8), febre (6/8), vômitos (5/8), anúria (4/8), urina escura (4/8), dores ósseas acompanhadas de mialgias (5/8) e icterícia (3/8). Quatro pacientes necessitaram tratamento dialítico, e três foram submetidos à biópsia renal que demonstrou Nefrite Rúbulo Intersticial Aguda. Os autores atribuem estas manifestaçöes ao uso intermitente da rifampicina e sugerem cuidados a serem observados quando se usa esquema multidroga (MDT)