Efeito da suplementação de colecalciferol nos RNA mensageiros urinários associados ao podócito em pacientes com doença renal crônica / Effect of cholecalciferol supplementation on urine podocyte-associated messenger RNAs in patients with chronic kidney disease

RESUMO Introdução: A vitamina D reduz a albuminúria em pacientes com doença renal crônica (DRC), mas o seu efeito sobre os podócitos glomerulares ainda não é claro. Objetivos: Avaliar se a suplementação de colecalciferol reduz os RNAm urinários associados ao podócito em pacientes com DRC. Métodos: Vinte e sete pacientes com DRC estágios 2 a 4 e níveis sub-ótimos de 25-hidroxi-vitamina D [25(OH)D] sérica foram tratados com colecalciferol por seis meses. Foram medidos antes e após a intervenção a 25(OH)D sérica e o RNAm urinário da nefrina, podocina, podocalixina, receptor transitório potencial do canal de cátions, subfamília C, membro 6 (TRPC6), fator A de crescimento do endotélio vascular (VEGF-A) e fator de crescimento transformador beta (TGF-β1). Resultados: A TFGe reduziu em média 4,71 mL/min/1,73 m2 (p = 0,010 vs. basal), sendo 28 ± 16 mL/min/1,73 m2 aos seis meses. Os RNAm dos produtos do podócito na urina não tiveram alteração significativa após o tratamento. Entretanto, pacientes que atingiram níveis de 25(OH)D ≥ 20 ng/mL aos 6 meses tiveram tendência de redução do RNAm da nefrina e da podocina na urina; nos pacientes em que a 25(OH)D permaneceu < 20 ng/mL houve aumento significativo da podocalixina, e tendência de maior expressão do RNAm da nefrina e da podocina. Conclusão: A reposição de colecalciferol por seis meses não teve efeito sobre os RNAm associados ao podócito nestes pacientes com DRC avançada. O efeito protetor da vitamina D ou seus análogos sobre o podócito glomerular deve ser investigado em estágios mais precoces da DRC e com maior tempo de tratamento.

ABSTRACT Introduction: Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. Objective: To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. Methods: A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months. Serum 25(OH)D level, estimated glomerular filtration rate (eGFR), proteinuria, and urine mRNA of nephrin, podocin, podocalyxin, transient receptor potential cation channel 6, vascular endothelial growth factor A, and transforming growth factor beta were assessed before and after intervention. Results: eGFR declined at an average rate of -4.71 mL/min/1.73 m2 (p = 0.010 vs. baseline), being 28 ± 16 mL/min/1.73 m2 at six months. No changes in proteinuria or mineral and bone metabolism parameters were observed after cholecalciferol supplementation. Urinary podocyte-associated mRNAs did not change significantly after treatment. However, patients who achieved 25(OH)D level > 20 ng/mL at six months showed a trend of reduction of urinary nephrin and podocin mRNA levels; in patients with 25(OH)D that remained < 20 ng/mL there was a significant increase in urinary podocalyxin, and a trend of higher expression of urinary nephrin and podocin mRNA. Conclusion: Six months of cholecalciferol supplementation had no effect on urine podocyte-associated mRNA profile of patients with advanced CKD. The protective effect of vitamin D or its analogues on the glomerular podocyte should be investigated in early stages of CKD with a longer treatment period.

Blood Urea & Salivary Urea levels in End Stage Renal Failure.

Elevation of Blood Urea Nitrogen in renal diseases results concomitant increase in Salivary Urea levels. Aims : Determine if there was any correlation between the Salivary Urea levels with that of Blood Urea levels. Material & Methods : samples of blood and saliva were taken from Hemodialysis and control groups to assess the Blood Urea Nitrogen (BUN) and Salivary Urea (SU) levels respectively under strict aseptic precautions. Informed consent was taken from patients and ethical committee approval taken. Results : showed no statistically significant difference between Blood Urea and Salivary Urea in the Hemodialysis group (p>0.05). There was a statistically significant difference between Hemodialysis group and Control group with respect to Blood Urea and Salivary Urea levels. (p<0.001). Conclusion : saliva can be used as a noninvasive diagnostic marker tool.

JC polyomavirus infection in candidates for kidney transplantation living in the Brazilian Amazon Region

This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation.

Preditores de insuficiência renal crônica em pacientes de centro de referência em hipertensão arterial / Predictors of chronic renal failure in patients of a hypertension center

OBJETIVO: Testar variáveis clínicas relacionadas à evolução para insuficiência renal crônica avaliadas rotineiramente em hipertensos e que possam ser utilizadas como instrumento preditivo, possibilitando seu acesso em qualquer nível de assistência. MÉTODOS: Foram avaliados 358 pacientes do Centro de Hipertensão Arterial da Faculdade de Medicina de Botucatu -UNESP. Destes, 210 apresentavam uma segunda avaliação da filtração glomerular e foram utilizados na análise. Aplicou-se regressão logística para identificar características clínicas que se associassem de maneira independente com o desfecho filtração glomerular final igual ou inferior a 60 ml/min. RESULTADOS: No total da casuística, apenas a proteinúria à urina I associou-se de maneira independente ao desfecho. Entre os 175 pacientes com filtração glomerular inicial superior a 60 ml/min, a presença de proteinúria à urina I, o gênero feminino e a idade igual ou superior a 50 anos foram preditores da evolução para filtração glomerular final igual ou inferior a 60 ml/min. CONCLUSÃO: A proteinúria avaliada à urina I foi um fator de risco associado ao desenvolvimento de insuficiência renal crônica independente de outros co-fatores analisados. Hipertensos primários com proteinúria à urina I devem receber atenção redobrada no sentido de prevenir a evolução para insuficiência renal crônica.

PURPOSE: to verify which clinical variables can predict the evolution to chronic renal insufficiency in routinely evaluated hypertensives. METHODS: 358 patients from the Hypertension Center of the Botucatu School of Medicine (São Paulo State University) were evaluated. Sequential evaluation of glomerular filtration rate was detected in 210 patients, who were analyzed. Logistic regression was applied to identify clinical variables independently associated with the development of chronic renal insufficiency with a final glomerular filtration rate equal to or below 60 ml/min. RESULTS: in routine urinalysis only proteinuria was independently associated with the outcome. Among 175 patients with initial glomerular filtration rate above 60 ml/min, proteinuria, female gender and age of 50 years or more were predictors of the evolution to a final glomerular filtration rate equal to or below 60 ml/min. CONCLUSION: the presence of proteinuria in simple urinalysis was a risk factor and a reliable predictor associated with the development of chronic renal insufficiency among hypertensives.

Spot morning urine protein creatinine ratio and 24 hour urinary total protein excretion rate.

Proteinuria helps to establish the diagnosis of most renal diseases and also to predict the outcome of such diseases. Proteinuria is biochemically represented by measuring the protein concentration in timed collection of 24 hour urine. But, 24-hour timed urine collection is time consuming, cumbersome and often unreliable due to collection errors and also results in undue delay on diagnostic process. An alternate approach avoiding arduous and inaccurate timed urine collection can be the measurement of protein creatinine ratio in spot morning urine. This study was aimed to evaluate whether the spot morning urine protein creatinine ratio can be a reliable alternative to 24-hour urinary total protein (UTP) estimation. The study was carried out in the department of Biochemistry, Bangabandhu Sheikh Mujib Medical University, Dhaka on 50 (fifty) non-diabetic Chronic Renal Disease (CRD) patients with an age ranging from 18 -70 years. The study subjects were grouped into mild, moderate and severe CRD on the basis of GFR. Urinary protein and creatinine concentrations were measured in spot morning urine samples and their ratios were calculated. Urinary protein measured in 24-hour timed collected urine samples gave the 24-hour UTP excretion rate. In our study, spot morning urine protein creatinine ratio significantly correlated with 24-hour UTP excretion rate in all CRD patients. Severe CRD patients gave significant positive correlation (p<0.05), whereas mild and moderate CRD patients gave very highly significant positive correlation (p<0.001). Therefore, it may be suggested that protein creatinine ratio in spot morning urine can be accepted as a reliable and alternative to 24-hour UTP excretion rate in non-diabetic chronic renal disease patients. This simple and inexpensive procedure will thus simplify the way of establishing the severity of renal disease along with its prognosis.

Insuficiencia renal en pacientes con trasplante hepatico: incidencia y factores predisponentes / Renal failure in patients with liver transplat: incidence and predisposing factors

En los pacientes que son sometidos a un trasplante hepático se desarrolla con frecuencia insuficiencia renal. Sin embargo, su incidencia y los factores predisponentes al desarrollo de esta complicación no han sido bien establecidos. Por tanto, nuestro estudio ha sido dirigido a clarificar ambos aspectos en pacientes que han sido sometidos a un trasplante hepático en el Hospital Italiano de Buenos Aires. Para ello, se evaluaron em forma retrospectiva 38 pacientes adulltos receptores de un trasplante hepático durante su estadía en el hospital (40 + 10 días) (media + DS). En el an lisis final se excluyeron 3 pacientes (1 hepatitis fulminante y 2 con sobrevida menor a 72 hs). El tratamiento inmunosupresor se basó en el triple esquema: ciclosporina, corticoides y azatioprina. La presencia de insuficiencia renal se definió como la existencia de una creatinina sérica > 1.5 mg/dl y/o urea > 80 mg/dl. La insuficiencia renal se clasificó cronológicamente como precoz (días 0-6) y tardia (luego del día 6). Los siguientes par metros fueron evaluados en relación a la insuficiencia hepática: preoperatoria (función hepatocelular mediante la clasificación de Chil-Pugh y renal), intraoperatorios (cantidad de hemoderivados transfundidos, episodios de hipotensión, "by-pass" venovenoso, duración de la cirugía y de la fase anhepática) y postoperatorios (sepsis, rechazo, niveles plasm ticos de ciclosporina y uso de drogas nefrotóxicas). En veintiuno de los 35 pacientes (60 por ciento) con trasplante hepático se desarrolló insuficiencia renal. En 6 pacientes fue precoz y en 15 tardía. En la serie global, los pacientes con insuficiencia renal presentaron un mayor deterioro de la función hepática en el preoperatorio (8.6 + 0.3 vs 7.8 + 0.4, p<0.05), en el intraoperatorio un mayor requerimiento de hemoderivados (13.1 + 4.3 vs 10.1 + 3.8 unidades, p<0.05) y en el postoperatorio in nivel más elevado de ciclosporina (624 + 60 vs 430 + 30 ng/ml, p<0.05) que aquellos pacientes en quienes no se desarrolló complicación. Asimismo, en los pacientes que presentaron la insuficiencia renal en forma precoz se observó un mayor deterioro de la función hepatocelular y un mayor requerimiento de hemoderivados durante la cirugía. De otra parte, en los pacientes que la desarrollaron en forma tardía, la etiopatogenia de esta complicación fue multifactorial (falla del injerto, uso de drogas nefrotóxicas y ciclosporina). En 1 paciente hubo necesidad de realizar hemodiálisis y en otro hemofiltración...

Ras oncoprotein level and urinary enzymes activity as sensitive indicators of renal injury in acute and chronic renal failure

Sixty-one patients with renal failure and ten healthy controls were included in this study. Patients were subdivided into three groups; group I included 20 patients with acute renal failure [ARF], group II included 20 patients with chronic renal failure [CRF] and group III included 21 patients with renal impairment [RI]. Serum ras oncoprotein was significantly higher in patients with ARF, CRF and RI compared with the controls. Ras oncoprotein level, sialic acid level and urinary excretion of the studied enzymes were not changed significantly with increased degrees of albuminuria or with the presence of casts, RBCs or pus cells in urine. Neither kidney size sonographically nor degree of echogenicity has an effect on the studied bioindices. The study revealed statistically significant correlations between ras oncogene expression and urinary enzymes excreted during renal damage

Asymptomatic bacteriuria in haemodialysis patients

This study was designed to assess the frequency significance and possible pathogenic factors of asymptomatic bacteriuria in chronic haemodialysis patients. A hundred patients suffering from endstage renal failure under regular haemodialysis treatment [divided into 3 groups according to the underlying cause of renal failure whether primary glomerulonephritis [forty cases] tubulointerstitial nephritis [thirty cases] or diabetic nephropathy [thirty cases] were randomely selected from the dialysis unit of Ain Shams University Hospital, El Sahil Teaching Hospital and Cairo Kidney Centre. None of these patients suffered symptoms nor signs suggestive of urinary tract infection and all were subjected to full history and clinical examination, clean catch midstream urine analysis with culture [aerobic and anaerobic]. Bacterial isolates were identified by bacteriological methods and sensitivity [when needed] in addition to microscopic examination for pus cells. Also, assessment of blood urea and serum creatinine were done. A subgroup of patients [proved to have asymptomatic bacteriuria 10 cases] as well as an equal subgroup of those having no significant bacteriuria were further studied by assessment of residual kidney function, total and differential WBCs counts, serum Ig[G], Ig[A] level, urinary Ig[A] level, opsonophagocytic function and migration inhibition test. Though we had high prevalence of significant bacteriuria in our patients [50%]. Pyuria was detected in only 14% of cases, all except one were associated with significant bacteriuria and the most prevalent organism was Staphylococcus aureus followed by Staph. saprophyticus. We didn't detect any significant correlation between significant bacteriuria and either age of the patients, duration, frequency of dialysis, blood urea or serum creatinine but female patients and chronic interstitial nephritis were associated with significant high prevalence of assymptomatic bacteriuria. In the two subgroups studied no correlation was detected between significant bacteriuria and either W.B.Cs count, residual kidney function, macrophage migration inhibition test, opsonophagocytic activity, Ig[A] or Ig[M] level. Though low Ig[G] level was associated with higher prevalence of asymptomatic bacteriuria. It is conducted that local factors may be more important than systemic factors in the pathogenesis of asymptomatic bacteriuria in haemodialysis patients and that routine urine analysis should be regularly performed in these patients to detect and possibly treat such cases especially female patients and cases of chronic interstitial nephritis