https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60687-X.pdf

Chronic kidney disease: global dimension and perspectives

Background Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. Methods In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. Results Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. Conclusions Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; RIVUR ClinicalTrials.gov number, NCT00405704.).

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Antimicrobial prophylaxis for children with vesicoureteral reflux.

Context: Although vitamin D toxicity is rare in children, increased use of vitamin D formulations, re-examination of optimal vitamin D levels, and use of higher doses lend potential for an increased incidence of vitamin D toxicity. Evidence Acquisition: A PubMed search was conducted through May 2013 for cases of vitamin D intoxication and vitamin D trials in pediatrics. Safety data were collected and reviewed. Evidence Synthesis: A small number of pediatric studies tested vitamin D doses at or above the currently recommended upper tolerable intake. In children and adolescents, vitamin D excess was rare and usually asymptomatic. Recent cases of intoxication relate to errors in manufacturing, formulation, or prescription; involve high total intake in the range of 240 000 to 4 500 000 IU; and present with severe hypercalcemia, hypercalciuria, or nephrocalcinosis. However, mild hypercalcemia and hypervitaminosis using currently recommended doses have been reported in infants with rickets. Conclusions: Althoug...

Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature.

This is a multi-centric randomized controlled trial [1] comparing cotrimoxazole prophylaxis versus no prophylaxis in children (<6 years old) with vesicoureteral reflux (VUR) detected after a first or second episode of urinary tract infection (UTI). The trial was designed to determine efficacy in preventing recurrence of UTI and renal scarring, as well as antibiotic resistance patterns. It was conducted across 19 sites in the United States, recruiting subjects over nearly five years, with follow-up for at least two years. Among 86% children who completed the study, the investigators observed lower recurrence of UTI in the intervention group (14.8%) in comparison to controls (27.4%). Intention-totreat analysis showed similar results but lesser magnitude of difference (25.5% vs 37.4%). However, there was no difference in the incidence of renal scarring (new scarring or worsening of pre-existing scarring); 11.9% and 10.2% in the intervention and control groups, respectively. The prevalence of antibiotic resistance increased significantly with prophylaxis. The investigators concluded that antibiotic prophylaxis is useful to prevent repeat episodes of UTI in children with VUR.

/pdf/antimicrobial-prophylaxis-for-children-with-vesicoureteral-4e42mbsmyh.pdf

The worldwide misuse of antibiotics and the subsequent rise of multidrug-resistant pathogenic bacteria have prompted a paradigm shift in the established view of antibiotic and bacterial-human relations. The clinical failures of conventional antibiotic therapies are associated with lengthy detection methods, poor penetration at infection sites, disruption of indigenous microflora and high potential for mutational resistance. One of the most promising strategies to improve the efficacy of antibiotics is to complex them with micro or nano delivery materials. Such materials/vehicles can shield antibiotics from enzyme deactivation, increasing the therapeutic effectiveness of the drug. Alternatively, drug-free nanomaterials that do not kill the pathogen but target virulent factors such as adhesins, toxins, or secretory systems can be used to minimize resistance and infection severity. The main objective of this review is to examine the potential of the aforementioned materials in the detection and treatment of antibiotic-resistant pathogenic organisms.

https://www.dovepress.com/getfile.php?fileID=47604

Recent advances in the treatment of pathogenic infections using antibiotics and nano-drug delivery vehicles.

Urinary tract infection (UTI) is the most common infection experienced by humans after respiratory and gastro-intestinal infections, and also the most common cause of both community-acquired and nosocomial infections for patients admitted to hospitals. For better management and prognosis, it is mandatory to know the possible site of infection, whether the infection is uncomplicated or complicated, re-infection or relapse, or treatment failure and its pathogenesis and risk factors. Asymptomatic bacteriuria is common in certain age groups and has different connotations. It needs to be treated and completely cured in pregnant women and preschool children. Reflux nephropathy in children could result in chronic kidney disease; otherwise, urinary tract infections do not play a major role in the pathogenesis of end-stage renal disease. Symptomatic urinary tract infections occur most commonly in women of child-bearing age. Cystitis predominates, but needs to be distinguished from acute urethral syndrome that affects both sexes and has a different management plan than UTIs. The prostatitis symptoms are much more common than bacterial prostatic infections. The treatment needs to be prolonged in bacterial prostatitis and as cure rates are not very high and relapses are common, the classification of prostatitis needs to be understood. The consensus conference convened by National Institute of Health added two more groups of patients, namely, chronic prostatitis/chronic pelvic pain syndrome and asymptomatic inflammatory prostatitis, in addition to acute and chronic bacterial prostatitis. Although white blood cells in urine signify inflammation, they do not always signify UTI. Quantitative cultures of urine provide definitive evidence of UTI. Imaging studies should be done 3-6 weeks after cure of acute infection to identify abnormalities predisposing to infection or renal damage or which may affect management. Treatment of cystitis in women should be a three-day course and if symptoms are prolonged, then a seven day course of antibiotics should be given. Selected group of patients benefits from low-dose prophylactic therapy. Upper urinary tract infection may need in-patient treatment. Treatment of acute prostatitis is 30-day therapy of appropriate antibiotics and for chronic bacterial prostatitis a low dose therapy for 6-12 months may be required. It should be noted that no attempt should be made to eradicate infection unless foreign bodies such as stones and catheters are removed and correctable urological abnormalities are taken care of. Treatment under such circumstances can result only in the emergence of resistant organisms and complicate therapy further.

Approach to urinary tract infections

Our study aimed to obtain a comprehensive insight into the etiology of nephrotic syndrome in our patient population. We analyzed medical records of 290 patients with diagnosis of nephrotic syndrome as defined by International Study of Kidney Disease in Children (ISKDC), between January 1987 and December 2000, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar. Primary glomerular disease was found to be the most prevalent, accounting for 91.73% of all glomerular diseases. Among primary glomerular diseases, minimal change disease (MCD) was the most common histological lesion (43.79%). Most patients presented within 3 months duration (61.4%) and the most common symptom was puffiness of face (98.45%) followed by pedal edema (91%). Focal segmental glomerulosclerosis (FSGS) was the second most common lesion (16.89%) followed by membranous glomerulonephritis (GN) (13.4%) and membranoproliferative GN (11.72%). Amongst secondary glomerular diseases, diabetes mellitus was the most prevalent (4.48%), followed by lupus nephritis (3.1%). In conclusion, primary glomerular diseases constituted the most common group encountered and the prevalence of MCD was quite high with males, children and young adults. FSGS was associated with a high prevalence of end-stage renal disease (ESRD; 26.53%), hypertension (71.42%) and hematuria (81.63%).

Etiological profile of nephrotic syndrome in Kashmir

A 70 year-old male presented with acute renal failure and mental obtundation. On examination, he was found to have hypercalcemia and on further questioning, it was found that it was secondary to injections of a slow-release vitamin D preparation. Although total body exposure is sufficient for vitamin D synthesis, increased vitamin D deficiency secondary to poor exposure to sunlight is observed in some parts of the world. We report here a case of vitamin D intoxication from the Kashmir valley where vitamin D deficiency is 100% in the general population that is confined indoors.

Vitamin D intoxication presenting as acute renal failure.

Human immunodeficiency virus (HIV) involves glomerular, tubulointerstitial, and vascular compartments of the kidney. The most common glomerular lesion is HIV-associated focal segmental glomerulosclerosis (FSGS) and related mesangiopathies collectively termed HIV-associated nephropathy (HIVAN). A variety of immune-complex mediated glomerular diseases such as membranoproliferative glomerulonephritis (MPGN), IgA nephropathy, and lupus-like glomerulonephritis also occur. HIVAN is restricted to patients presenting with proteinuria and progressive reduction of renal function and with distinctive but not pathognomonic pathology (FSGS often coexisting with glomerular collapse and tubular microcystic dilatations). The worldwide incidence of collapsing glomerulopathy (CG) in HIV-positive patients is high in Americans. But in India and other Asian countries, other forms of kidney diseases are more commonly seen. We report the first case of CG in the state of Jammu and Kashmir which also happens to be a very low incidence belt for HIV.

M S Najar

Papers

Approach to urinary tract infections

Etiological profile of nephrotic syndrome in Kashmir

Vitamin D intoxication presenting as acute renal failure.

Collapsing glomerulopathy in an HIV-positive patient in a low-incidence belt.