Clinical profile of children with posterior urethral valve at Tertiary Care Center.

Background & Objective: Posterior Urethral Valves (PUV) are common cause of congenital obstructive uropathy in boys and may be associated with urinary tract infection(UTI) and chronic kidney disease(CKD) if not managed timely. The objective of our study was to determine the clinical profile of children with PUV. Methods: This is a descriptive case series comprising of 30 children aged 1-5 years, diagnosed and managed as PUV over six months, conducted at the Department of Pediatric Nephrology, National Institute of Child Health, Karachi. Patients were followed for 12 weeks and the outcome was assessed in terms of recovery, UTI, urinary incontinence and CKD. Descriptive statics were used for data analysis. Results: Thirty cases of PUV were managed during study period. Clinical presentations were poor urinary stream (83%), fever (73%), signs and symptom suggesting UTI (96.6%), pallor (73.3%), acute kidney injury (37%)and urinary retention (13%). UTI was confirmed in 73.3 % and E.Coli was the most common pathogen. Ultrasonography showed bilateral hydronephrosis/hydroureter in 80% and micturating cystourethrogram demonstrated vesicoureteral reflux in 86.66% cases. All patients received intravenous hydration (97%), urinary decompression, and antibiotics. Meropenem was the most commonly used. Packed cell transfusion and peritoneal dialysis was done in 73.33% and 13.3% respectively. Cystoscopic valve fulguration was done in 86.66% and vesicostomy in 13.3%. On short-term follow-up, 60% recovered,16.66% experienced UTI and remained incontinent whereas 23.33% had CKD. Conclusion: Our study showed a high frequency of UTI and AKI. E. coli was most common pathogen. Despite valve fulgration, significant patients had CKD.

Safety and Adequacy of Ultrasound-Guided Percutaneous Renal Biopsy in Children: A Single-Center Experience.

Background Ultrasound-guided percutaneous renal biopsy (PCRB) is a commonly used technique to obtain renal tissue for histopathological diagnosis in children and adolescents. The objectives of this study include determining the indications for renal biopsy, documenting the safety and efficacy of ultrasound-guided PCRB, and documenting its complications along with histopathological findings in children. Methodology The Ethical Review Committee approved this cross-sectional study. Data of all children with either nephrotic or nephritic syndrome from January 2017 to September 2020 (at The Kidney Center Post Graduate Training Institute Karachi) who underwent ultrasound-guided PCRB were collected and analyzed. An ultrasonic examination was performed both before and after the biopsy. Results During the research period, 104 individuals underwent PCRB. The average age of the children biopsied was 7.44 ± 4.12 years (range = 1-17 years). The most prevalent reason for biopsy was nephrotic syndrome. Almost 94% of PCRBs were effective. Post-biopsy complications were detected in 16 cases, with peri-nephric hematoma being the most prevalent. Conclusions In children, ultrasound-guided PCRB can safely be performed under sedation in experienced hands with an automated biopsy gun needle. The use of real-time ultrasound guidance as well as the automated biopsy gun ensures good outcomes.

Etiology, Clinical Profile, and Short-Term Outcome of Children With Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome in hospitalized children and it imposes heavy burden of mortality and morbidity. In resource-constraint settings, management of AKI is very challenging and associated with adverse outcomes. The aim of this study was to determine the clinico-etiological profile and outcome of AKI. METHODOLOGY: This prospective observational study was done at the department of pediatric nephrology and pediatric intensive care unit, National Institute of Child Health, Karachi, Pakistan from December 2020 to May 2021. A total of 130 children aged 1 month to 15 years, diagnosed with AKI irrespective of the underlying cause were included. Detailed medical information of each child including medical history, examination, and baseline investigations were obtained. Clinical and etiological profile of patients was noted. The patients were followed up to three months and the outcome was noted. RESULTS: In a total of 130 children, 82 (63.1%) were male. The mean age was 5.5±4.4 years (ranging between 1 month and 15 years). There were 117 (90.0%) children who were referred from other centers for either dialysis or surgical treatment. Prerenal cause of AKI was found in 66 (50.8%) children, followed by renal 53 (40.8%) and postrenal in 11 (8.5%) cases. Fever and shortness of breath were the most common clinical presenting symptoms in 102 (78.5%) and 100 (76%) cases, respectively. There were 45 (34.6%) cases who were managed conservatively, 80 (61.5%) needed dialysis, while three children were managed with plasmapheresis and two required surgical intervention in the emergency department. At three-month follow-up period, 64 (49.2%) children recovered (including nine with partial recovery), 46 (36.1%) expired, 9 (6.9%) developed end-stage renal disease, while 11 (8.5%) had chronic kidney disease. CONCLUSION: Sepsis, nephrotoxic drugs, and acute glomerulonephritis were the major causes of AKI at our center. Mortality was high among children presenting with AKI. A relatively high proportion of children with younger age, septic AKI, and presentation in critical condition could be the reasons for this high mortality.

Rapidly progressive glomerulonephritis in children.

Rapidly progressive glomerulonephritis (RPGN), characterized by a rapid development of nephritis with loss of kidney function in days or weeks, is typically associated histologically, with crescents in most glomeruli; and is a challenging problem, particularly in low resource settings. RPGN is a diagnostic and therapeutic emergency requiring prompt evaluation and treatment to prevent poor outcomes. Histopathologically, RPGN consists of four major categories, anti-glomerular basement membrane (GBM) disease, immune complex mediated, pauci-immune disorders and idiopathic /overlap disorders. Clinical manifestations include gross hematuria, proteinuria, oliguria, hypertension and edema. Diagnostic evaluation, including renal function tests, electrolytes, urinalysis/microscopy and serology including (anti GBM antibody, antineutrophil cytoplasmic antibody (ANCA)) starts simultaneously with management. An urgent renal biopsy is required to allow specific pathologic diagnosis as well as to assess disease activity and chronicity to guide specific treatment. The current guidelines for management of pediatric RPGN are adopted from adult experience and consist of induction and maintenance therapy. Aggressive combination immunosuppression has markedly improved outcomes, however, nephrotic syndrome, severe acute kidney injury requiring dialysis, presence of fibrous crescents and chronicity are predictors of poor renal survival. RPGN associated post infectious glomerulonephritis (PIGN) usually has good prognosis in children without immunosuppression whereas immune-complex-mediated GN and lupus nephritis (LN) are associated with poor prognosis with development of end stage kidney disease (ESKD) in more than 50% and 30% respectively. Given the need for prompt diagnosis and urgent treatment to avoid devastating outcomes, we conducted a review of the latest evidence in RPGN management to help formulate clinical practice guidance for children in our setting. Information sources and search strategy: The search strategy was performed in the digital databases of PubMed, Cochrane Library, google scholar, from their inception dates to December 2020. Three investigators independently performed a systematic search using the following search terms "Rapidly progressive glomerulonephritis" "children" "crescentic glomerulonephritis" "management" at the same time, backtracking search for references of related literature.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Efficacy of Levamisole in children with Frequent Relapsing and Steroid Dependent Nephrotic Syndrome at Tertiary Care Center-Karachi.

OBJECTIVES: To determine the effectiveness of levamisole in maintaining remission of proteinuria in children with frequent relapsing and steroid dependent nephrotic syndrome (FR/SDNS). METHODS: This observational study on 81 children with FR /SDNS was carried out from June 2007 - June 2017 at The Kidney Center-Postgraduate Training Institute, Karachi-Pakistan. Levamisole (leva) along with low dose prednisolone on alternate day (AD) was used after induction of remission with daily oral prednisolone in children with FR/ SDNS for 6-36 months. Patients with steroid resistance were excluded. Data was analyzed using descriptive statistics. RESULTS: Eighty-one patients with FR (66) or SD (15) received levamisole treatment. Mean age at diagnosis was 3.72 ±2.33 years. Levamisole was used on AD in 59.25% and daily in 40.74% of cases. Twenty-four could not complete six months and were excluded, 57 patients completed treatment duration of 15.68±9.93 months and 51 post-leva follow-up of 11.70±11.23 months. Mean leva-dose was 1.73±0.67 mg/kg/ patient. Mean cumulative prednisolone dose per patient before, on-leva and post-leva was 3389.81±2785.22, 2471.97±2024.98 and 661.37± 905.37 mg respectively. Mean relapse rate per year before leva, on -leva and post -leva was 3.30 ±0.50,0.98± 1.1and 0.79±1.27 respectively. Levamisole was effective in 90% of patients. During post-leva follow up, 76.4% patients, maintained remission, whereas 23.5% behaved as FR/SD and require further immunosuppressive therapy. CONCLUSIONS: Levamisole was effective in maintaining remission in 90% while on treatment, whereas it maintained remission after discontinuation in 76.4% cases. Levamisole may be used as first steroid sparing agent before other immunosuppressive therapies in children with FR/SDNS. Further studies are required for optimal duration and dosage schedule.

Pediatric Continuous Renal Replacement Therapy (PCRRT) expert committee recommendation on prescribing prolonged intermittent renal replacement therapy (PIRRT) in critically ill children.

INTRODUCTION: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost-effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting. METHODS: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles. The Pediatric Continuous Renal Replacement Therapy workgroup analyzed all articles for relevancy, proposed recommendations, and graded each recommendation for their strength of evidence. RESULTS: Of the 60 studies eligible for review, the workgroup considered data from 37 studies to formulate guidelines for the use of PIRRT in children. The guidelines focused on the definition, indications, machines, and prescription of PIRRT. CONCLUSION: Although the literature on the use of PIRRT in children is limited, the current studies give credence to their benefits and these expert recommendations are a valuable first step in the continued study of PIRRT in the pediatric population.

Tumor lysis syndrome in pediatric acute lymphoblastic leukemia at tertiary care center.

OBJECTIVES: Tumor lysis syndrome (TLS) is common complication of acute lymphoblastic leukemia (ALL). It is characterized by presence of two or more of hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia. TLS may cause acute kidney injury (AKI), arrhythmias and seizures. Our objective was to determine the frequency of TLS and its biochemical abnormalities in children with ALL. METHODS: A retrospective study on 91 children, aged 2-13 years with ALL was carried out in Nephrology and Oncology departments of National Institute of Child Health, Karachi from January 2016 to December 2017. Patients already received chemotherapy were excluded. Data including risk categories, immunophenotyping, laboratory parameters like complete blood picture, serum creatinine (SCr), potassium(K), calcium (Ca), phosphorus(P) and uric acid (UA) on day 0,3 and 7 after chemotherapy were collected. Data analyzed on SPSS using descriptive statistics. Independent t- test was applied to compare means and P- value<0.05 was taken as significant. RESULTS: Ninety-one children with mean age of 6.39±3.08 years were studied. Male were 57% and 43% female. High risk ALL were 61.5%. Pre -BALL were 82.4% and 17.5% had T-cell ALL. All patients had anemia (hemoglobin7.69±2.66 g/dl) and thrombocytopenia (43.61± 18.6 x109) where as hyperleukocytosis and blast cells were observed in 20.87% and 73.6% respectively. Comparing the biochemical parameters of ALL, the difference in SCr from D0 vs D3 (0.46±0.16 vs0.54± 0.35 and D7, 0.44±0.22) was significant (p=0.001). Similarly, difference in UA (D0, 4.12±2.40 vs D3, 3.82±1.73 and D7, 3.56±1.42), SP (D0, 4.24±1.34 vs D3, 4.61±1.76 and D7,4.13±1.07mg/dl)and for K (p=0.038) was significant. There was no difference in Ca from D0 vs D3 (0.092) and D7 (0.277). TLS was found in 62.6% children, it was chemotherapy induced in 72% and spontaneous in 28%. Clinical-TLS was observed in 14% and all CTLS had AKI. Hyperuricemia and hyperphosphatemia were the most common biochemical abnormalities in laboratory-TLS and CTLS. CONCLUSION: TLS was found in 62.6% despite preventive measures. Early recognition and treatment is essential to avoid morbidity and mortality.

Immunosuppressive therapy in children with primary nephrotic syndrome: single center experience, Karachi, Pakistan.

BACKGROUND: Majority of children with nephrotic syndrome are steroid sensitive, but treatment of difficult to treat nephrotic (frequent relapsing, steroid dependent and steroid resistant) syndrome is challenging. Low dose steroid, levamisole, cyclophosphamide (CPM), mycophenolate mofetil (MMF) and calcineurin inhibitors (CNIs) are the common options of treatment. Objective of the study was to determine the response to steroid and alternative immunosuppressive agents (ISAs) in children with difficult nephrotic syndrome (DNS). METHODS: This is a retrospective cohort study of 176 children with DNS, managed over 12 years at The Kidney Center-Postgraduate Training Institute, Karachi- Pakistan from 2005 to 2017. Initial episode was treated with daily oral prednisolone (OP) for 4-8 weeks followed by alternate day OP for 12-24 weeks. Subsequently low dose OP, levamisole (Leva)and cyclophosphamide was used for frequent relapsing (FR)/ steroid dependent (SD). All with initial steroid resistance and non- responders to leva and or cyclophosphamide were biopsied and treated with CNIs and MMF. Data was analyzed using descriptive statistics. RESULTS: There were 130(73.86%) children with FR/SD and 46(26.13%) with SRNS. All children with SR (46) and 86 with FR/SD were biopsied. Minimal change disease (60.60%) and focal segmental glomerulosclerosis (FSGS 23%) were the two common lesions. Majority (73.86%) received single OP whereas divided doses were administered in 26.13% cases. Daily OP was used for 4, 6 and 8 weeks in 61.36,28.4 and10.22% respectively. Steroids were tapered over 3 (31.81%),4 (52.27%) and 6 months (15.90%). Levamisole, CPM, cyclosporin (CS) and MMF were used sequentially in 45, 54.23, 50 and 20% respectively. Combination of MMF and CS was used in 11.29% of cases. Levamisole was effective in 80%, CPM induced complete remission (CR, 57.77%) or partial remission (PR, 22.22%), CS induced CR 46.59% and PR 39.77%. MMF showed PR and CR 69 and 12.82% respectively. At last follow up, 46% were maintaining remission while off treatment, whereas 35% are maintaining remission on therapy,10.23% lost- to-follow, 5.68% progressed to chronic kidney disease. Mortality was 2.84% and it was due to infection and uremia. CONCLUSION: Majority had steroid sensitive MCD. Levamisole and cyclophosphamide were effective in maintaining remission in FR/ SD. FSGS was responsible for resistance to steroid and alternative ISAs. Cyclosporin was effective in inducing remission in SRNS. Mortality was less than 3%.

Vitamin D status in under five children in diverse communities of Karachi.

BACKGROUND & OBJECTIVE: Vitamin D deficiency (VDD) prevalence is very high in pediatric population in developing countries including Pakistan. VDD contribute significantly to morbidity and mortality among children under five years. Therefore, it is vital to study vitamin D levels in population for future interventions and disease control. Our objective was to determine 25(OH)D levels in children of one to 59 months of age in socio-economically diverse communities of Karachi, Pakistan. METHODS: The cross- sectional analytical survey was carried out over 6 months from January -June 2017. Following proportionate sampling technique four clusters were randomly selected from Korangi, Saddar, Sindhi para and Manzoor colony, Karachi. Blood samples for 25(OH)D and zinc levels were carried out using ELISA and colorimetry. VD level <20 ng/ml was defined as VDD and serum zinc <65ug/dl as low zinc levels. Data including area of residency, gender, ethnicity, parent's education, family income, house status, duration of sun exposure and history of VD and zinc intake in last 3 months was collected from parents / care seekers on pretested and pre-coded semi-structured questionnaire. Data was analyzed using SPSS version-20. Frequencies and percentages were computed for categorical variables like gender, type of malnutrition whereas mean with standard deviation was used for VD and zinc levels and vitamin D status was compared in three different residential categories according to nutritional status. RESULTS: Out of 120 children, 67 (56%) were boys and 53 (44%) girls. Mean VD level was 22.8±14.8 ng/ml. Around 60% (70) children were VD deficient, whereas 15 % (18) had insufficient 25(OH)D levels. VDD was more prevalent among low socio-economic group with no obvious difference in age category. Mean zinc level was 123.8±47.45 ug/dl and it was either normal or high (42%) rather than low. Malnutrition was observed in 65% children and majority (82%) of them were undernourished. Optimal sun exposure was reported in 24% children only. CONCLUSION: Vitamin D deficiency was highly prevalent in our study population. Children of low socio-economic strata and with sub-optimal sun light exposure are at high risk of vitamin D deficiency. Unexpectedly, high zinc levels in majority of our children with low VD status needs further evidence to substantiate this inverse relation.

Infantile Spasms: Clinical profile and treatment outcomes.

BACKGROUND AND OBJECTIVE: Infantile spasm (IS) is one of the severe epileptic encephalopathies which affect children in early two years of life. Our objective was to determine the clinical profile, etiology and outcome of treatment in children with infantile spasms attending tertiary care hospital at Karachi, Pakistan. METHODS: This is retrospective study of 36 patients out of 94 registered as IS, aged three months to two years, managed and followed up at Aga Khan University Hospital, Karachi, from 2010 to 2015. Data of all children with IS was collected from case record. Details including clinical observations, lab investigations, anti-epileptic medications and treatment outcome was collected and analyzed. Patients who received treatment for six weeks to document response were included. The treatment response was categorized as complete response, partial response (>50% improvement) and no response. Data was analyzed on SPSS using descriptive statistics. RESULTS: Thirty- six patients (38.29%) with IS fulfilled eligibility criteria. The mean ± SD age at presentation was 4.6±2.1 months. Male to female ratio was 2:1. Consanguinity and developmental motor delay was observed in 66.6% and 89% respectively. Symptomatic etiology was predominant (61%) and hypoxic ischemic insult (32%) was the commonest underlying cause. EEG and MRI were diagnostic tools whereas metabolic studies were not helpful. Multiple antiepileptic drugs were used for seizure control and vigabatrin was the most frequently used (88%) drug. Short term treatment response was not different in idiopathic or symptomatic infantile spasms. CONCLUSION: Majority of patients had symptomatic infantile spasms and generalized tonic clonic along with myoclonic jerks were predominant seizure types. EEG and MRI were diagnostic in most of cases. Multiple AEDs were required to control seizures and VGB was most common drug (88%) used. Treatment outcome was not different in idiopathic and symptomatic groups.

Comparison of three formulae for estimation of glomerular filtration rate in severely malnourished children at tertiary care facility.

OBJECTIVES: First objective was to compare eGFR by Updated Schwartz (US) and Simple Height Independent (SHID) formula with Original Schwartz (OS) in children with Severe Acute Malnutrition (SAM). The second objective was to compare eGFR in children below and above two years. METHODS: This analytic study on estimation of GFR was based on retrospective data collected from 78 children with SAM at Nutritional Rehabilitation Unit from October 2014 - March 2015. Glomerular filtration rate was calculated using serum creatinine (S. Cr) and height in Original Schwartz, US and by age in SHID equation and compared with OS as standard. Data was analyzed using descriptive statistics. RESULTS: There were 78 children in this study. Males were 39(50%). Mean age of patients was 18±15.53 months with 62(79.48%) ≤24 months. Mean weight, height and Mid Upper Arm Cir-cumference was 5.69±2.42kg, 68.52+13.59 cm and 10±1.57 cm respectively. Mean eGFR by OS, US and SHID formula was 71.45±49.89, 58.06±3.91 and 59.33±3.73ml/min/1.73m2 respectively. There was significant difference (0.001) in mean eGFR calculated by three different formulae. Majority of children (73%) had subnormal GFR (<90 ml/min /1.73 m2). There was a significant difference in GFR ≥90ml calculated by US compared to OS (0.025) and by SHID with OS (0.04) in children below two years and no difference in children above two years. But there was no difference in other categories of eGFR calculated by either of formula in both age groups. CONCLUSION: We found a significant difference in eGFR in ranges above 90 ml/min/1.73 m2 by US compared to OS as well as by SHID with OS in children below two years and no difference in children above two years. Also, there was no difference in GFR categories below 90 ml/min /1.73 m2 calculated by either of formula in both age groups. So, we may conclude that either of formula can be used in clinical practice for eGFR in mild to severe renal dysfunction in severely malnour-ished children.

Functional and structural abnormalities of the kidney and urinary tract in severely malnourished children - A hospital based study.

OBJECTIVES: The association of malnutrition and systemic diseases like chronic kidney disease (CKD) is well known. Various urinary tract abnormalities may be associated with malnutrition. So objective of current study was to determine the frequency of functional and structural urinary tract abnormalities in severely malnourished children admitted in Nutritional Rehabilitation Unit (NRU) of a tertiary care facility, Karachi. METHODS: This descriptive cases series of 78 children was conducted in NRU from October 2014 - March 2015. All newly admitted children aged 2-60 months, diagnosed as Severe Acute Malnutrition (SAM) were studied and children with known kidney and urinary tract disorders were excluded. Detailed history, examination and investigations like serum creatinine, ultrasound kidney and urinary tract in addition to routine tests for SAM, were done. A proforma was used to collect demographic data, clinical history, physical findings, and radio-imaging and biochemical investigations. Glomerular filtration rate (GFR) was calculated using Schwartz equation. Data was analyzed using descriptive statistics. RESULTS: Among 78 children, male to female ratio was equal. Mean age was 18±15.53 months and majority (79.48%) of children were below 24 months. Majority (82%) of children with SAM had marasmus whereas 18% had edematous malnutrition. Out of 78, 57 (73%) children had either functional (80.7%) and or structural (19.3%) abnormalities whereas 21(36.84%) had normal functional and structural status. Most common functional abnormality was subnormal GFR (<90ml/min/1.73 m2) found in all 46 children. Functional abnormities were more common in children below 24 months. Other functional disorders were Bartter syndrome, renal tubular acidosis and urinary tract infection (UTI) found in two cases each. Common structural abnormalities were echogenic kidneys (n=4, 36%), hydronephrosis (n=3, 27%), hypoplastic kidneys (n=3, 27%) and calculi (n=1, 9%). Subnormal GFR was also found in all cases with structural abnormalities. UTI was observed exclusively in two children among 11 with structural abnormalities. CONCLUSION: A high frequency of functional abnormalities and noticeable proportion of structural abnormalities of urinary tract were detected in children with SAM. Current finding suggest that multicenter study at national level may be undertaken to generate better data about prevalence of renal diseases in SAM.

Frequency of Stillbirths in a Tertiary Care Hospital, Karachi.

BACKGROUND AND OBJECTIVE: Pakistan accounts for the highest stillbirth rate in the world. Therefore, this observational study was planned to determine the prevalence of stillbirths and its associated demographic characteristics in the given context. Hence our objective included: To determine the frequency of stillbirths with reference to parity and gestational age in a tertiary care public hospital, Karachi. To determine the socio-demographic characteristics of families with stillbirths. METHODS: All pregnant mothers who delivered stillbirth babies at Gynaecology and Obstetrics ward of Jinnah Postgraduate Medical Center, Karachi a tertiary care facility were prospectively enrolled from October 2012 to September 2013. Deliveries occurred before 28 weeks of gestational age were excluded. Gestational age was confirmed from hospital record and attending physicians. Data was collected on predesigned proforma and analyzed using descriptive statistics. RESULTS: Among 7708 registered deliveries, 137 were stillbirths. A total of 84 mothers were primiparous and 12% of mothers were below 20 years at the time of delivery. Majority of stillbirths were macerated type (80.3%) and 20% were fresh stillbirth. About 55% of still births occurred between 33-37 weeks and 20% between 28-32 weeks. Almost 80% (109) of stillbirths were low birth weight and only 20% (28) were normal birth weight. CONCLUSION: This study shows that stillbirths are more common in primiparous mothers in a given context. Conducting awareness sessions with special focus on antenatal and obstetrical care of primiparous may be helpful to reduce still births.

Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.

Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.

Zinc supplement in reduction of relapses in children with steroid sensitive nephrotic syndrome.

OBJECTIVE: To determine whether Zinc supplementation could reduce relapse rate in children with nephrotic syndrome. STUDY DESIGN: Randomized-controlled trial. PLACE AND DURATION OF STUDY: National Institute of Child-Health and The Kidney Centre, Karachi, from January 2008 to June 2009. METHODOLOGY: Sixty nephrotic children aged 2 - 15 years were selected. Baseline data including age, number of infections and relapses during pre and post study one year were recorded. Randomization was done to divide into Zinc group (Zg) to receive Zinc versus placebo (Pg) for 6 months. Relapses and infections were treated with standard therapy. T-test and chi-square tests were used to compare the mean values and proportions respectively with significance at p < 0.05. RESULTS: Among 60 children, 54 completed trial (Zg = 25, Pg = 29). Forty (74%) were males and 14 (26%) females. Mean age, pre study relapses and Zinc level in the two groups were similar. Overall, infections and relapses were observed in 43 (79.62%) and 17 cases (31.48%) respectively. There was no significant difference in frequency of infections and mean infection rate in Zg (20, 80% and 1.92 ± 1.47) compared to Pg (23, 79.3% and 2 ± 1.53, p = 0.950). Relapses occurred in 7 (28%) in Zg compared to 10 (34%) in Pg which was not significant (p = 0.609). Mean infection and relapse rate per patient per year (PPPY) in Zg was 1.92 ± 1.47and 1.14 ± 0.37 compared to 2 ± 1.53 and1.3 ± 0.48 in Pg respectively (p=0.846, 0.464). Pre study relapses in two groups were similar (Zg vs. Pg = 96 vs. 96.6%) whereas post study relapses in Zg were lower (7, 28%) compared to Pg (10, 34.5%). Post study mean relapse rate in Zg was 1.14 ± 0.37 PPPY compared to 2.71 ± 1.11 in pre study (p = 0.005). In Pg, post study mean relapse rate PPPY was 1.30 ± 0.48 compared to 1.70 ± 0.48 in pre study period (p = 0.037). Relapse rate reduction was 43% after Zinc supplementation compared to 27% reduction in placebo. Metallic taste was observed in 10% of cases. CONCLUSION: Zinc supplementation was helpful in reducing relapses in nephrotic syndrome.

Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans.

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

Parenteral iron sucrose in iron deficiency anaemia of paediatric chronic kidney disease.

BACKGROUND: Erythropoietin (Epo) and iron therapy plays a major role in the management of renal anaemia. Iron sucrose (IS) has been used to treat iron deficiency anaemia (IDA) and to maintain adequate iron store in chronic kidney disease (CKD). The objective of the study was to determine the response and safety of IS in the treatment of IDA. METHODS: This retrospective study was carried out in the Department of Nephrology, National Institute of Child Health, Karachi from Dec 2008 to Dec 2010. Children aged 6 months to 14 years, CKD-stage 2-5, and IDA were included. Pertinent data including age, gender, serum creatinine (SCr), CKD-stage, aetiology, treatment mode, IS dose, pre- and posttreatment parameters and side effects were collected and analysed. RESULTS: Among 35, majority (66%) were boys. Mean age was 6.97 +/- 4.13 years and mean SCr was 3.78 +/- 3.1 mg/dl. Majority were in CKD-stage 4-5 and treated conservatively. Major aetiologies were hypoplasia-dysplasia (40%), juvenile nephronophthiasis (17.14%), posterior urethral valves, and stones. Baseline mean Hb and Transferrin Saturation (TS) was 7.38 +/- 1.38 g/dl and 11.19 +/- 5.28% respectively. Mean Hb increased to 9.22 +/- 16.32 g/dl with correction of iron deficit (p<0.001) and a sustained rise in Hb was observed after Epo and maintenance iron sucrose. Mean TS% increased to 49.13 +/- 18% (p<0.001). No major side effects were observed except iron overload. CONCLUSION: Iron sucrose was effective in improving IDA in CKD without significant side effects. Iron sucrose may be used to treat IDA with monitoring for iron overload.

Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS).

BACKGROUND: Recessive mutations in the NPHS1 gene encoding nephrin account for approximately 40% of infants with congenital nephrotic syndrome (CNS). CNS is defined as steroid-resistant nephrotic syndrome (SRNS) within the first 90 days of life. Currently, more than 119 different mutations of NPHS1 have been published affecting most exons. METHODS: We here performed mutational analysis of NPHS1 in a worldwide cohort of 67 children from 62 different families with CNS. RESULTS: We found bi-allelic mutations in 36 of the 62 families (58%) confirming in a worldwide cohort that about one-half of CNS is caused by NPHS1 mutations. In 26 families, mutations were homozygous, and in 10, they were compound heterozygous. In an additional nine patients from eight families, only one heterozygous mutation was detected. We detected 37 different mutations. Nineteen of the 37 were novel mutations (approximately 51.4%), including 11 missense mutations, 4 splice-site mutations, 3 nonsense mutations and 1 small deletion. In an additional patient with later manifestation, we discovered two further novel mutations, including the first one affecting a glycosylation site of nephrin. CONCLUSIONS: Our data hereby expand the spectrum of known mutations by 17.6%. Surprisingly, out of the two siblings with the homozygous novel mutation L587R in NPHS1, only one developed nephrotic syndrome before the age of 90 days, while the other one did not manifest until the age of 2 years. Both siblings also unexpectedly experienced an episode of partial remission upon steroid treatment.

Histopathological pattern in childhood glomerulonephritis.

OBJECTIVES: To determine the histopathological pattern in childhood glomerulonephritis (CGN). METHODS: This retrospective analysis of renal biopsies of 118 children with various clinical syndromes of CGN was carried out at the National Institute of Child Health (NICH) and The Kidney Center (TKC), Karachi, from July 2005 to December 2009. The age ranged from 6 months to 16 years. All biopsies were studied under light microscopy (LM) and immunoflourescence (IMF). Histopathological lesions (HPL) were classified as primary and secondary glomerular diseases. Demographic data, indications and HPL were retrieved and analyzed using descriptive statistics. RESULTS: Out of 118 patients, 62 (52.54%) were males and 56(47.45%) females. Mean age was 8.2 +/- 3.9 years. Major indications for biopsy were primary nephrotic syndrome (PNS 86, 72.88%). secondary GN (SGN, 17, 14.4%) and nephritic-nephrotic syndrome (NNS 13, 11%). Overall, primary glomerular diseases (PGD) accounted for 84.74% of all biopsies. Minimal change disease (MCD 38, 32.2%) and focal segmental glomerulosclerosis (FSGS 35, 29.66%) were the two most common lesions and accounted for 43% and 33.72% respectively in PNS. Other important lesions were membranous GN (MGN 10, 8.47%), membranoproliferative (MPGN 9, 7.16%), post-infective (PIGN 4, 3.38%) and IgM nephropathy (IgMN 3, 2.54%). Among secondary glomerular diseases (SGD), lupus nephritis (LN 11, 9.32%) was the most common lesion followed by Henoch-Schonlein nephritis (HSN) and haemolytic uraemic syndrome (HUS) each in 3 (2.52%). CONCLUSION: Overall, MCD and FSGS were the two most common HPL in PGD and both dominated in PNS. Lupus nephritis was the leading lesion in SGD. These histopathological pattern of CGN in our study is in conformity with the existing literature from Pakistan.