[Pathological peculiarities of chronic kidney disease in patient from sub-Saharan Africa. Review of data from the Democratic Republic of the Congo]. / Particularités anatomopathologiques de la maladie rénale du sujet de l'Afrique sub-Saharienne : revue synthétique des données de la République démocratique du Congo.

Chronic kidney disease (CKD) is a major global public health problem. But kidney involvement is more common and appears more severe in Africa than in developed countries. The likely causes of end stage renal disease (ESRD) or CKD stage 3 and above in developed countries are diabetes, hypertension and less frequently glomerular diseases. In contrast, in decreasing order in Africa are glomerulopathies, hypertension and diabetes. The reasons for this preponderance of glomerular diseases are not fully known but may be linked to the persistence or reemergence of tropical diseases. This study reviews the kidney involvements more associated with common tropical diseases including HIV/AIDS. The most common HIV/AIDS lesion is a specific focal and segmental glomerulosclerosis (FSGS) termed HIV-associated nephropathy (HIV-AN). Renal complications of tropical parasites are heterogenous. Various glomerulopathies like FSGS occur during various filariasis infections. Schistosoma mansoni is responsible for membranoproliferative glomerulonephritis and amyloidosis. Human African trypanosomiasis is associated with cryoglobulinemic membranoproliferative glomerulonephritis. The Plasmodium malariae is mainly responsible for membranoproliferative glomerulonephritis. Acute patterns (acute tubular necrosis or acute postinfectious glomerulonephritis) are observed during Plasmodium falciparum infection. Several other viral, bacterial or mycobacterial infections like leprosy and tuberculosis still prevalent in Africa can also affect the kidney. Sickle cell disease is responsible for a variety of renal injuries. In conclusion, kidney lesions linked to tropical diseases partly explain the peculiar pattern of CKD of the black race and play a significant role in the current outbreak of the CKD in Subsaharan Africa.

Renal dysfunction in leprosy: a historical cohort of 923 patients in Brazil.

We investigated the factors associated with renal dysfunction in leprosy patients from Brazil. We report on a historical cohort of leprosy patients followed in two hospitals in Fortaleza City in northeastern Brazil. The factors associated with renal dysfunction were investigated. A total of 923 patients were included, with a mean age of 41.5 ± 19.1 years, and 53.3% were male. Renal dysfunction was found in 35 cases (3.8%). Proteinuria was found in 4.8% of cases, haematuria in 6.8% and leukocyturia in 10.4%. Factors associated with renal dysfunction by multivariate analysis were: reaction episode (odds ratio [OR] = 3.9, P = 0.03), multibacillary classification (OR = 3.5, P = 0.02) and advanced age (OR = 1.04, P = 0.01). Four patients (0.4%) died. Leprosy is associated with renal dysfunction, especially in older patients and those presenting with reaction episode and multibacillary classification.

Clinical pharmacokinetics of thalidomide.

Thalidomide is a racemic glutamic acid derivative approved in the US for erythema nodosum leprosum, a complication of leprosy. In addition, its use in various inflammatory and oncologic conditions is being investigated. Thalidomide interconverts between the (R)- and (S)-enantiomers in plasma, with protein binding of 55% and 65%, respectively. More than 90% of the absorbed drug is excreted in the urine and faeces within 48 hours. Thalidomide is minimally metabolised by the liver, but is spontaneously hydrolysed into numerous renally excreted products. After a single oral dose of thalidomide 200 mg (as the US-approved capsule formulation) in healthy volunteers, absorption is slow and extensive, resulting in a peak concentration (C(max)) of 1-2 mg/L at 3-4 hours after administration, absorption lag time of 30 minutes, total exposure (AUC( infinity )) of 18 mg. h/L, apparent elimination half-life of 6 hours and apparent systemic clearance of 10 L/h. Thalidomide pharmacokinetics are best described by a one-compartment model with first-order absorption and elimination. Because of the low solubility of the drug in the gastrointestinal tract, thalidomide exhibits absorption rate-limited pharmacokinetics (the 'flip-flop' phenomenon), with its elimination rate being faster than its absorption rate. The apparent elimination half-life of 6 hours therefore represents absorption, not elimination. The 'true' apparent volume of distribution was estimated to be 16L by use of the faster elimination-rate half-life. Multiple doses of thalidomide 200 mg/day over 21 days cause no change in the pharmacokinetics, with a steady-state C(max) (C(ss)(max)) of 1.2 mg/L. Simulation of 400 and 800 mg/day also shows no accumulation, with C(ss)(max) of 3.5 and 6.0 mg/L, respectively. Multiple-dose studies in cancer patients show pharmacokinetics comparable with those in healthy populations at similar dosages. Thalidomide exhibits a dose-proportional increase in AUC at doses from 50 to 400 mg. Because of the low solubility of thalidomide, C(max) is less than proportional to dose, and t(max) is prolonged with increasing dose. Age, sex and smoking have no effect on the pharmacokinetics of thalidomide, and the effect of food is minimal. Thalidomide does not alter the pharmacokinetics of oral contraceptives, and is also unlikely to interact with warfarin and grapefruit juice. Since thalidomide is mainly hydrolysed and passively excreted, its pharmacokinetics are not expected to change in patients with impaired liver or kidney function.

Lepra lepromatosa, fenómeno de Lucio, paniculitis mixta más vasculitis y daño renal

El fenómeno de Lucio es una leprorreacción necrotizante infreceunte que ocurre en la forma de lepra lepromatosa difusa e infiltrativa conocida como lepra de Lucio. Se presenta el caso de un paciente con lepra de Lucio quien en el transcurso de su enfermedad desarrolló glomerulonefritis proliferaliva, fenómeno de Lucio y eritema nodoso leproso. se consiguió una evolución terapéutica satisfactoria con farmacoterapia triconjugada convencional asociada con esteroides sintémicos

Role of reactive oxygen species in renal damage in experimental leprosy.

Renal involvement is known to occur in leprosy. In the present study the possible role of reactive oxygen species (ROS) in causation of renal damage in mice infected with Mycobacterium leprae has been investigated. At least six animals from each group (control and infected) were killed at 0 day, 3, 6 and 9 months postinfection. The results showed a significant increase in the chemiluminescence (CL) response of peritoneal macrophages which was maximum between 3 and 6 months. No significant increase was observed in CL response of blood neutrophils. A significant increase in lipid peroxidation was observed at 3 and 6 months as evident by an increase in malondialdehyde levels. The increased ROS production might be the cause of lipid peroxidation. The renal damage is alos evident by decrease in the activity of renal brush border membrane enzymes, namely, alkaline phosphatase, leucine aminopeptidase and r-glutamyl transpeptidase. Thus ROS might play a role during early stages of M. leprae infection but in the later stages other immunological mechanisms may overpower the effect of ROS.

Sequential renal functions in leprosy.

Sequential renal functions have been studied in eight patients of lepromatous leprosy during and after subsidence of erythema nodosum leprosum. The renal functions which were impaired during reaction were observed to improve during quiescent phase unless there were associated complications like amyloidosis. The possible mechanisms for altered renal functions during reactive phase of the disease have been discussed.

Sequential renal functions in leprosy

Sequential renal functions have been studied in eight patients of lepromatous leprosy during and after subsidence of erythema nodosum leprosum. The renal functions which were impaired during reaction were observed to improve during quiescent phase unless there were associated complications like amyloidosis. The possible mechanisms for altered renal functions during reactive phase of the disease have been discussed.