Absence of clinical abnormalities suggesting renal involvement during the long-term course of visceral Leishmaniasis

Abnormalities of renal function have been demonstrated inpatients with visceral leishmaniasis; although there was a trend toward normalization following antiparasitic therapy, some abnormalities persisted. With thepurpose of studying the long- term clinical course of renal involvement in visceral leishmaniasis, 32 patients with a diagnosis of this parasitic disease were evaluated in the endemic area and at least 6 months after the clinical cure of the disease and compared with a control group of 28 individuals. No patient had a history or clinical findings suggestive of renal disease and all were normotensive. Laboratory evaluation was normal in all except 3 patients with abnormal urinalysis. Mild proteinuria and microscopic hematuria were seen in a single urinalysis in one patient (although three other urinalysis were normal), and leucocyturia in two female patients. It was concluded that the renal involvement in visceral leishmaniasis is mild and transient, with normal renal function observed on long-term follow-up after cure of the parasitic infection.

Prevalência de anemia e insuficiência renal em portadores de insuficiência cardíaca não-hospitalizados

FUNDAMENTOS: Insuficiência cardíaca (IC) é uma doença comum com alta taxa de mortalidade. Anemia e insuficiência renal (IR) são frequentemente encontradas em portadores de IC associadas com maior gravidade da doença cardíaca e pior prognóstico. OBJETIVO: Avaliar a prevalência de anemia e insuficiência renal, bem como a associação entre esses dois quadros, em portadores de IC não hospitalizados. MÉTODOS: Foram observados pacientes acompanhandos na clínica de IC de um hospital universitário de julho de 2003 a novembro de 2006. Anemia foi definida como níveis de hemoglobina abaixo de 13 mg/dl para homens e de 12 mg/dl para mulheres. A função renal foi avaliada por meio da taxa de filtração glomerular (TFG), calculada pela fórmula simplificada do estudo MDRD (Modification of Diet in Renal Disease). RESULTADOS: Dos trezentos e quarenta e cinco pacientes incluídos neste estudo, 26,4% (n = 91) tinham anemia e 29,6% tinham insuficiência renal moderada a grave (TFG < 60 ml/min). A associação entre anemia e maior prevalência de insuficiência renal foi estatisticamente significante (41,8% vs. 25,2%; p = 0,005). Os pacientes em classe funcional III e IV apresentaram maior incidência de anemia (39,0% vs. 19,4%; p <0,001) e insuficiência renal (38,2% vs. 24,8%; p = 0,007). Não foi observada associação entre anemia ou insuficiência renal e história de hipertensão, diabetes, função sistólica ou etiologia de insuficiência cardíaca. CONCLUSÃO: A prevalência de anemia e insuficiência renal foi elevada nessa população e foi associada com a gravidade da insuficiência cardíaca (classes funcionais III e IV).

Disfunção renal e anemia em pacientes com insuficiência cardíaca com fração de ejeção reduzida versus normal

FUNDAMENTO: A presença de anemia e de disfunção renal confere mau prognóstico em pacientes com insuficiência cardíaca (IC) e fração de ejeção reduzida (ICFER). O impacto em pacientes com IC e fração de ejeção normal (ICFEN) é pouco estudado. OBJETIVOS: Estudar a prevalência e o prognóstico da anemia e da disfunção renal (DR) em pacientes com IC de acordo com o tipo de disfunção ventricular. MÉTODOS: Foram estudados prospectivamente 209 pacientes com IC crônica estável. Pacientes com fração de ejeção <50 % foram considerados como tendo ICFER. Anemia foi definida pelos critérios da OMS como hemoglobina <13 g/dl em homens e <12 g/dl em mulheres. A função renal foi calculada pela fórmula sMDRD (Simplified Modified Diet Renal Disease). Hospitalizações, visitas a emergências e óbitos por causas cardíacas foram considerados como eventos cardíacos. RESULTADOS: Noventa pacientes tinham ICFER e 119, ICFEN. A taxa de filtração glomerular (TFG) foi menor no grupo com ICFER (57,6 ± 66,2 versus 94,8 ± 36,6 ml/min/1,73m²; p=0,01). Não houve diferença na prevalência da anemia nos dois grupos (23,3% versus 18,5%; p=0,34). A prevalência da DR moderada a grave foi maior no grupo com ICFER (32,2% versus 16,8% p=0,01). A DR foi o único fator associado à anemia e associou-se independentemente com eventos cardíacos (HR 2,52; IC 95% = 1,27 - 5,2; p=0,01). CONCLUSÃO: DR foi menos prevalente na ICFEN, enquanto a prevalência de anemia não diferiu entre os dois grupos. A DR foi preditora de eventos cardíacos, independentemente da fração de ejeção.

Disfunção renal e marcadores inflamatórios em hipertensos atendidos em hospital universitário

FUNDAMENTO: A doença renal crônica representa hoje um grande desafio para a saúde pública no sentido de se obterem conhecimentos para subsidiar intervenções que possam alterar a velocidade de perda da função renal. OBJETIVO: Avaliar a magnitude do déficit da função renal em hipertensos adultos e sua relação com marcadores inflamatórios: proteína C reativa ultrassensível, velocidade de hemossedimentação e relação neutrófilos/linfócitos. MÉTODOS: Estudo transversal envolvendo 1.273 adultos hipertensos, de ambos os sexos, sendo 1.052 com déficit da função renal e 221 sem déficit, diagnosticados pela equação Modification of Diet in the Renal Disease. A razão de chances (OR) e a razão de prevalência (RP) foram utilizadas para determinar a probabilidade de ocorrência de atividade inflamatória na doença renal. RESULTADOS: O déficit de função renal foi diagnosticado em 82,6% dos avaliados, sendo que a maioria da amostra (70,8%) estava inserida no estágio 2 da doença renal crônica. No modelo de regressão permaneceram independentemente associadas ao déficit da função renal a síndrome metabólica (RPajustada = 1,09 [IC95%: 1,04-1,14]), a proteína C reativa ultrassensível (RPajustada = 1,54 [IC95%: 1,40-1,69]) e a velocidade de hemossedimentação (RPajustada = 1,20 [IC95%: 1,12-1,28]). No entanto, considerando os indivíduos classificados no estágio 2 do déficit da função renal, a chance de alteração dos marcadores inflamatórios foram de OR = 10,25 (IC95%: 7,00-15,05) para a proteína C reativa ultrassensível, OR = 8,50 (IC95%: 5.70-12.71) para a relação neutrófilos/linfócitos e OR = 7,18 (IC95%: 4,87-10,61) para a velocidade de hemossedimentação. CONCLUSÃO: Os resultados mostram associação da atividade inflamatória e da síndrome metabólica com o déficit da função renal.

Impaired renal function in owl monkeys (Aotus nancymai) infected with Plasmodium falciparum

Impaired renal function was observed in sixteen Aotus nancymai 25 and 3 months following infection with the Uganda Palo Alto strain of Plasmodium falciparum. Decrease were noted in the clearance of endogenous creatinine, creatinine excretion, and urine volume while increases were observed in serum urea nitrogen, urine protein, urine potassium, fractional excretion of phosphorus and potassium, and activities of urinary enzymes. The results were suggestive of glomerulonephropathy and chronic renal disease.

Serum intact parathyroid hormone levels in cats with chronic kidney disease

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha), IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-ß (TGF-ß) using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

Cultural adaptation and validation of the "Kidney Disease and Quality of Life - Short Form (KDQOL-SF™ 1.3)" in Brazil

The objective of the present study was to translate the Kidney Disease Quality of Life - Short Form (KDQOL-SF™1.3) questionnaire into Portuguese to adapt it culturally and validate it for the Brazilian population. The KDQOL-SF was translated into Portuguese and back-translated twice into English. Patient difficulties in understanding the questionnaire were evaluated by a panel of experts and solved. Measurement properties such as reliability and validity were determined by applying the questionnaire to 94 end-stage renal disease patients on chronic dialysis. The Nottingham Health Profile Questionnaire, the Karnofsky Performance Scale and the Kidney Disease Questionnaire were administered to test validity. Some activities included in the original instrument were considered to be incompatible with the activities usually performed by the Brazilian population and were replaced. The mean scores for the 19 components of the KDQOL-SF questionnaire in Portuguese ranged from 22 to 91. The components "Social support" and "Dialysis staff encouragement" had the highest scores (86.7 and 90.8, respectively). The test-retest reliability and the inter-observer reliability of the instrument were evaluated by the intraclass correlation coefficient. The coefficients for both reliability tests were statistically significant for all scales of the KDQOL-SF (P < 0.001), ranging from 0.492 to 0.936 for test-retest reliability and from 0.337 to 0.994 for inter-observer reliability. The Cronbach's alpha coefficient was higher than 0.80 for most of components. The Portuguese version of the KDQOL-SF questionnaire proved to be valid and reliable for the evaluation of quality of life of Brazilian patients with end-stage renal disease on chronic dialysis.

The role of stress-activated protein kinase signaling in renal pathophysiology

Two major stress-activated protein kinases are the p38 mitogen-activated protein kinase (MAPK) and the c-Jun amino terminal kinase (JNK). p38 and JNK are widely expressed in different cell types in various tissues and can be activated by a diverse range of stimuli. Signaling through p38 and JNK is critical for embryonic development. In adult kidney, p38 and JNK signaling is evident in a restricted pattern suggesting a normal physiological role. Marked activation of both p38 and JNK pathways occurs in human renal disease, including glomerulonephritis, diabetic nephropathy and acute renal failure. Administration of small molecule inhibitors of p38 and JNK has been shown to provide protection from renal injury in different types of experimental kidney disease through inhibition of renal inflammation, fibrosis, and apoptosis. In particular, a role for JNK signaling has been identified in macrophage activation resulting in up-regulation of pro-inflammatory mediators and the induction of renal injury. The ability to provide renal protection by blocking either p38 or JNK indicates a lack of redundancy for these two signaling pathways despite their activation by common stimuli. Therefore, the stress-activated protein kinases, p38 and JNK, are promising candidates for therapeutic intervention in human renal diseases.

Raising awareness of chronic kidney disease in a Brazilian urban population

The incidence and prevalence of chronic kidney disease have been increasing in recent years in developing countries. The aim of this study was to report the results of a general chronic kidney disease awareness program applied to an urban population in a large Brazilian city. From January 2002 to January 2005 a total of 8883 individuals in the city of Curitiba (PR, Brazil) were screened for hypertension, body mass index, hematuria, and proteinuria. A family history and previous medical diagnosis of hypertension and diabetes mellitus (DM) were also recorded. Of the 8883 individuals assessed, 56% were women, subject median age was 47 years (range: 17-93 years) and more than 90% were Caucasian. Thirty percent had signs of hematuria, 6% had proteinuria, and 3% had hematuria and proteinuria. The median of mean arterial pressure values was 93 mmHg (range: 71-135 mmHg) and 16% of the population screened had a history of hypertension. A significant positive family history of both hypertension or DM was present in 42% (P < 0.0001; chi-square = 83.18) and 7% (P < 0.0001; chi-square = 161.31) of the hypertensive group, respectively. Finally, the prevalence of hypertension and DM was significantly higher in older individuals with proteinuria. In the present study, a higher prevalence of hematuria and proteinuria was found in older individuals with hypertension and diabetes compared to the general population. These data confirm the need for public awareness of renal disease in high-risk individuals.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 ± 10.1 years and 313 (37.2%) patients were males. MetS was detected in 662 (78.6%) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 ± 30.8; two: 92.9 ± 28.1; three: 84.0 ± 25.1; four: 83.8 ± 28.5, and five: 79.0 ± 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL·min-1·1.73 (m²)-1) 2.82-fold (95%CI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95%CI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95%CI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR) and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

Frequency of primary glomerular disease in northeastern China

Most frequently reported Chinese renal biopsy data have originated from southeastern China. The present study analyzed the renal biopsy data from northeastern China. The records of 1550 consecutive native patients who were diagnosed with primary glomerular diseases (PGD) after renal biopsy at our hospital during 2005-2009 were used. These patients were divided into four age groups for stratified analysis: <15, 15-44, 45-59, and ≥60 years old. Among PGD, minimal change disease (MCD) was the most common histologically diagnosed disease (30.7%), followed by IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MsPGN), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), and endocapillary proliferative glomerulonephritis (EnPGN). MCD was the disease most frequently observed (43.7%) in the <15-year-old group. MsPGN was the most common disease in the elderly group (38.1%). MsPGN was more prevalent in females (27.8%), whereas MCD was more prevalent in males (35.3%). Primary glomerular diseases constituted the most commonly encountered group of diseases with a high prevalence of MCD, which predominantly affected males and young adults. The prevalence of MCD was high in northeastern China. Further study is necessary to expand the epidemiologic data available for renal disease in China.

Chronic kidney disease in disadvantaged populations

The increased burden of chronic kidney disease (CKD) in disadvantaged populations is due to both global factors and population-specific issues. Low socioeconomic status and poor access to care contribute to health care disparities and exacerbate the negative effects of genetic or biological predisposition. Provision of appropriate renal care to these populations requires a two-pronged approach: expanding the reach of dialysis through development of low-cost alternatives that can be practiced in remote locations, and implementation and evaluation of cost-effective prevention strategies. Kidney transplantation should be promoted by expansion of deceased donor transplant programs and use of inexpensive, generic immunosuppressive drugs. The message of World Kidney Day 2015 is that a concerted attack against the diseases that lead to end-stage renal disease, by increasing community outreach, better education, improved economic opportunity, and access to preventive medicine for those at highest risk, could end the unacceptable relationship between CKD and disadvantage in these communities.

Evaluation of metabolic syndrome and associations with inflammation and graft function in renal transplant recipients

INTRODUCTION: Cardiovascular disease (CVD) is a major determinant of mortality in renal transplant recipients (RTR). Metabolic syndrome (MS) and chronic inflammation are currently considered non traditional risk factors for cardiovascular disease. This study evaluates the frequency of these conditions their associations with graft function. OBJECTIVE: To evaluate the prevalence of metabolic syndrome (MS) and inflammation and their associations with graft function in renal transplant recipients. METHODS: A cross-sectional study was carried out with 200 RTR. MS was defined by the NCEP-ATP III criteria. Inflammation was assessed by CRP levels. Renal function was assessed by GFR estimation using the MDRD equation. RESULTS: MS occurred in 71 patients (35.5%). Patients with MS had higher CPR and decreased GFR levels. Inflammation was present in 99 patients (49.5%). Mean waist perimeter, body mass index, triglycerides and serum total cholesterol were significantly higher in inflamed patients. An association between MS and inflammation was demonstrated, 48 (67.6%) patients with MS were inflamed and among those without MS the rate of inflamed patients was 39.5% (51 patients) (p < 0.001). A significantly higher percentage of patients with MS in the group of patients in chronic renal disease stages III and IV was observed. CONCLUSION: In RTR there is a significant association among MS and inflammation. MS is negatively associated with graft function. The clinical implications of these findings must be evaluated in longitudinal studies.