Aliskiren and losartan study in non-diabetic CKD: a comparison of patients in the clinical trial versus the usual care group

Background: This is a comparative study of a 6 year retrospective analysis of the therapeutic efficacy and safety of Combined Aliskiren (150 mg a day) and Losartan (100 mg a day) in a Clinical Trial setting versus a Usual Care group of patients on Losartan (100 mg a day), Telmisartan (80 mg a day) and Combined Enalapril (10 mg a day) plus Losartan (100mg a day) in non-Diabetic Chronic Kidney Disease (CKD) patients. The objective of this study was to ascertain if there were any differences in the renal outcome of patients treated within a Clinical Trial setting versus a Usual Care setting. The study seeks to establish the relevance of having a Usual Care group as a comparator and whether its inclusion in the study would help to validate the findings in the Clinical Trial group Methods: This is a 2nd Phase follow up study three years after the initial 1st Phase study in the Clinical Trial Group. Patients in the 2nd Phase study were those who continued to have proteinuria and were treated with Losartan 100mg a day. The 2nd Phase study seeks to document the incidence of remission of proteinuria following their initial 1st Phase therapy for proteinuria compared to those in the Usual Care group where treatment remained unchanged from year 1 to end of year 6. The rates of remission of proteinuria and improvement of renal function as well as associated comorbidities between the 2 groups are compared. Results: Among the 154 patients in the Clinical Trial Group, 70/154 (45%) continued to have proteinuria, while 84/154 (55%) had no proteinuria (remission) compared to 41 (28%) in remission and 104 (72%) with continued proteinuria in the Usual Care group (p<0.001). There were more patients with hypertension and yperkalaemia in the Clinical Trial group compared to the Usual Care group. Seven patients were in ESRF in the Usual Care group compared to only 3 in the Clinical Trial group but this difference was not significant. More patients in the Clinical Trial group compared to the Usual Care group had improvement in eGFR at the end of the 6 years (p<0.001). Conclusions: This study shows that patients in a Clinical Trial setting do better than those in the Usual Care setting as they are more likely to have improvement in renal function with remission of proteinuria.

significance of tubular and glomerular proteinuria in critically ill patients with severe acute kidney injury

Critically ill patients with acute kidney injury [AKI] frequently need acute renal replacement therapy [aRRT]. We evaluated an inexpensive, rapid quantitative and qualitative analysis of proteinuria on the course of AKI patients requiring aRRT in intensive care. This was a prospective, observational study of critically ill patients with severe established AKI or Acute on Chronic Kidney Injury [AoCKI] requiring aRRT. Urine samples were analyzed using Sodium-Dodecyl-Sulphate-Polyacryamide Gel Electrophoresis [SDS-PAGE]. A total of 30 critically ill patients were studied. Those who died have higher APACHE II [29 +/- 6 vs. 20 +/- 5, p<0.001], multi-organ failure [0.7 +/- 0.5 vs. 0.2 +/- 0.4, p < 0.02] and Tubular/Glomerular ratio [114 +/- 60 vs. 75 +/- 37, p < 0.05]. The renal non-recoverers have higher baseline creatinine [415 +/- 328 vs. 125 +/- 19 umol/l, p < 0.01], urinary Dipstick value [1.8 +/- 0.8 vs. 0.5 +/- 0, p <0.05] and Glomerular score [3.0 +/- 1.8 vs. 0.6 +/- 0.2, p < 0.02]. Heavy tubular proteinuria also predicts a longer duration of interim dialysis support and mortality whereas glomerular proteinuria correlates with development of chronicity and End Stage Renal Disease [ESRD]. The dominant presence of tubular proteinuria is associated with poor survival in patients who have high APACHE II score and multi-organ failure. It also correlates with a longer duration of dialysis support in survivals. Renal Non-recoverers had heavy dominant presence of glomerular proteinuria. SDS-PAGE proteinuria analysis offers a reliable and inexpensive method to prognosticate proteinuria in this group of critically ill patients

Genomics and disease progression in IgA nephritis

Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.

National Health Survey on the prevalence of urinary abnormalities in the population: then and now (1975 to 2012)

<p><b>INTRODUCTION</b>This paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries.</p><p><b>MATERIALS AND METHODS</b>The study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population.</p><p><b>RESULTS</b>In the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%.</p><p><b>DISCUSSION</b>The consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD.</p><p><b>CONCLUSION</b>The prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.</p>