Correlation of lymphocyte subsets and inflammatory biomarkers with disease severity in COVID-19 patients.

Objective: To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection. METHODS: The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20. RESULTS: Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037). Conclusion: Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.

Providing "Free" Access to Dialysis and Transplant to the Disfranchised. A Sustainable Model for Low and Low Middle Income Countries (LMICs).

Pakistan is a low-middle income country where incidence of End Stage Kidney Disease (ESKD) is 100-150 per million population (pmp). Paucity and high costs of renal replacement therapy (RRT) renders the majority disfranchised, since the dialysis rate is 15 pmp and the transplant rate is 4-5 pmp. In view of this, our center started an integrated dialysis and transplant program where all treatment is provided "Free of Cost" to all patients, with lifelong follow-up and medications. The model is based on the concept of community-government partnership funded by both partners. The annual contribution in 2021 was $37.4 million. >1,500 patients were dialyzed daily, and 6-8 received transplants weekly. Of the 6,553 transplants performed between 1985-2021, 988 (15%) were children. Overall, the 1 and 5-year graft survival rate was 97% and 88%. The donor clinic has 3,786 donors in regular yearly follow-up for up to 30-35 years where ESKD prevalence is 0.29%. Access to dialysis was increased by establishing six satellite centers reducing patient time and travel costs. Cost reductions by dialyzer reuse and generic drugs resulted in an annual saving of $5.8 m. This sustainable model has overcome the inherent socio-economic, logistic, cultural, and gender biases in RRT in LMICs. It has provided RRT with equity to the disfranchised in Pakistan and can be replicated in other LMICs with community-government support.

The pattern of RNA integrity and the expression of housekeeping genes are influenced by sodium hypochlorite and ascorbic acid.

BACKGROUND: Basic biological science research deals with nucleic acid isolation. Post-isolation nucleic acid integrity has a pivotal role in further elucidating gene expression and other molecular mechanisms. RNA (ribonucleic acid), cDNA (complementary deoxyribonucleic acid), and PCR (Polymerase chain reaction) products' integrity and quality are affected by several factors in biochemical and biophysical degradation modes. Inadequate evidence was noted about the direct effects of sodium hypochlorite and L-ascorbic acid. OBJECTIVES: This study aims to test the effects of sodium hypochlorite (SHC) and L-ascorbic acid (LAA) in total RNA and PCR products, respectively, in an acellular condition. METHODS: The study was categorized into three steps total RNA, cDNA, and PCR product evaluations. mBM-MSCs were used to extract RNA and then treated with SHC. Crude total RNA and, after DNase 1 treatment, the bands of total RNA samples were visualized by agarose gel electrophoresis. cDNAs were synthesized from SHC-treated (0.25%) and untreated RNAs, which were also expressed on the gel. LAA (5 µM, 15 µM, 25 µM, and 50 µM) were added to cDNAs synthesized from SHC- and non-SHC-treated samples. Housekeeping genes, Gapdh (Glyceraldehyde 3-phosphate dehydrogenase), and 18S rRNA (18S Ribosomal ribonucleic acid) were amplified in both groups. RESULTS: SHC-treated samples produced clearer bands on an agarose gel. Its treatment did not affect the integrated densities of agarose bands which revealed non-significant (P ≤ 0.05) differences in SHC-treated, untreated RNA, and cDNA. However, significant variations were observed at the PCR level. SHC-treated samples expressed decreased housekeeping gene expression in amplified products (Gapdh and 18S rRNA) and slightly but non-significantly high band intensities appeared in the presence of LAA. Significant variable differences (*P ≤ 0.05) were observed between SHC-treated and non-treated groups after LAA treatment. CONCLUSIONS: SHC (0.25%) is favorable in removing RNases and maintaining the integrity of RNA. cDNA synthesis did not affect by SHC treatment, and it follows the same as untreated samples after DNase 1 treatment. LAA drew a positive impact to improve the quality of PCR products in terms of band intensities, which is insignificant in SHC-treated RNA. Interestingly, it was revealed from our study that 5-25 µM LAA has the most beneficial role in the acquisition of PCR products, i.e. gene expression. These concentrations can be safely used to improve the quality of gene expression. This phenomenon can be used to achieve other, rarer, desired gene expressions. Further research is needed to explore the effects of SHC on the acquisition of PCR products using other solutions.

Outcomes of Cystectomy with MAINZ Pouch II and Epispadias Repair in Exstrophy Epispadias Complex in Adults: A Single-centre Experience from Pakistan.

OBJECTIVE: To evaluate surgical outcomes and renal functions after cystectomy + MAINZ Pouch II and epispadias repair as a staged procedure in adult patients with exstrophy epispadias complex (EEC). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Urology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, from January 2004 to December 2020. METHODOLOGY: A total of 33 patients with EEC were treated. Out of which, 20 underwent cystectomy + MAINZ Pouch II with epispadias repair as a staged procedure. Out of these, 17 had a follow-up period of more than a year and were included in the study. The patients were followed up after 6 weeks of surgery, at 6 months, one year, and at the end of follow-up. The assessed variables included the patients' renal function tests, malignancy potential, morning erections, ejaculations, night emissions, day-and-night-time urinary frequency, and overall happiness of patients at the end of follow-up. RESULTS: The mean age was 25.1 ± 7.5 years and mean follow-up duration was 7.8 ± 5.2 years. Postoperatively, there was a rise in blood urea from 27.8 to 35.08 mg/dl with a concurrent fall in serum bicarbonate from a mean of 23.5 to 20.2 mEq/dl. All patients were continent during the day-time postoperatively; whereas, two patients experienced nocturnal enuresis. All male patients exhibited good erections and ejaculations, but there was persistence of dorsal chordae in 4 (23.3%) patients. All were delighted, happy and pleased with the surgical outcomes and had returned to normal life. No rectal or sigmoid malignancy was observed. CONCLUSION: In adult EEC patients, cystectomy + MAINZ Pouch II and epispadias repair is safe and effective. Key Words: Adults, Exstrophy epispadias complex, MAINZ pouch II, Pakistan.

Stricture of Urethra: Patterns and Outcomes of Management from a Single Centre in Pakistan Over 7 Years.

OBJECTIVE: To determine the outcomes of urethroplasty and its complications from a large cohort of patients managed in a single centre. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Urology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, from January 2010 to December 2016. METHODOLOGY: A total of 546 patients with stricture urethra at different locations underwent urethroplasty from January 2010 to December 2016 were included. All patients had an ascending urethrogram followed by retrograde ± antegrade urethroscopy to assess the location and length of the stricture. Technique of urethroplasty was chosen according to the site, length and etiology. Following appropriate procedure, patients were followed up in the dedicated urethral stricture clinic. Procedure was considered successful if either no further therapeutic intervention was required and the maximum flow rate (Qmax) was >20 ml/sec with a voided volume of at least 200 mls. The procedure was regarded as unsuccessful, if further treatment was required or Qmax was <10ml/sec. RESULTS: A total of 546 patients with mean age of 32.3 +13.1 years (range: 12-74) involving anterior (n=323, 59.2%) or posterior (n=223, 40.8%) urethra were treated. Mean follow-up was 43.6 months (range: 3-84). The success rates of bulbar urethral strictures after excision and primary anastomosis (EPA) was 93. 3%, non-transecting urethroplasty 84.6% and oral mucosal graft (OMG), 81.8%. In penile urethral strictures, OMG, Orandi procedure and Johanson's techniques yielded success rates of 88.4%, 66.6% and 57.1%, respectively. In posterior urethral strictures, after excision and bulboprostatic anastomosis, good results were seen in 88.3%. In pan-urethral strictures, abdominal skin graft repair, combined tissue transfer and OMG urethroplasty yielded success rates of 74%, 78.5% and 75%, respectively. The complications/ adverse events were encountered in 251 / 546 (45.9%) patients in this series. CONCLUSION: Anastomotic urethroplasty yielded best outcomes followed by OMG urethroplasty. In the long-term follow-up, erectile dysfunction (ED), infertility and recurrence of stricture are the main complications which need individualised management.

Update on Surgical Management of Pediatric Urolithiasis.

Urolithiasis has always been a fascinating disease, even more so in children. There are many intriguing facets to this pathology. This article is a nonsystematic review to provide an update on the surgical management of pediatric urolithiasis. It highlights the pros and cons of various minimally invasive surgical options such as extracorporeal shockwave lithotripsy (ESWL), retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), laparoscopy, and robotics. This article also describes the various intracorporeal disintegration technologies available to fragment the stone, including the newer advancements in laser technology. It also emphasizes the cost considerations especially with reference to the emerging economies. Thus, this manuscript guides how to select the least-invasive option for an individual patient, considering age and gender; stone size, location, and composition; and facilities and expertise available.

Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: In regenerative medicine, mesenchymal stem cells derived from adipose tissues (Ad-MSCs) are a very attractive target to treat many diseases. In relation to nephrology, the aim of the current study is to investigate the effects of Ad-MSCs for the amelioration of acute kidney injury and to explore the mechanism of renal parenchymal changes in response to allogeneic transplantation of Ad-MSCs. METHODS AND RESULTS: The nephrotoxicity was induced by cisplatin (CP) in balb/c mice according to RIFLE Class and AKIN Stage 3. PCR, qRT-PCR and fluorescent labeled cells infusion, histopathology, immunohistochemistry, functional analyses were used for genes and proteins expressions data acquisition respectively. We demonstrated that single intravenous infusion of 2.5×107/kg mAd-MSCs in mice pre-injected with CP recruited to the kidney, restored the renal structure, and function, which resulted in progressive survival of mice. The renal tissue morphology was recovered in terms of diminished necrosis or epithelial cells damage, protein casts formation, infiltration of inflammatory cells, tubular dilatation, and restoration of brush border protein; Megalin and decreased Kim-1 expressions in mAd-MSCs transplanted mice. Significant reduction in serum creatinine with slashed urea and urinary protein levels were observed. Anti-BrdU staining displayed enhanced tubular cells proliferation. Predominantly, downgrade expressions of TNF-α and TGF-ß1 were observed post seven days in mAd-MSCs transplanted mice. CONCLUSIONS: Ad-MSCs exerts pro-proliferative, anti-inflammatory, and anti-fibrotic effects. Ad-MSCs transplantation without any chemical or genetic manipulation can provide the evidence of therapeutic strategy for the origin of regeneration and overall an improved survival of the system in functionally deprived failed kidneys.

Composition of urinary calculi in infants: a report from an endemic country.

Pediatric urolithiasis remains endemic in low-resource countries where infants constitute 17-40% of all children with urolithiasis. This study reports socio-economic factors, medical history and chemical composition of urinary stones in 976 infants of up to 2 years of age. Between 1992 and 2016, 976 infants presented to our institute with 1038 stones. Chemical composition of stones was analyzed by Fourier transformation infrared spectroscopy (FTIR). The mean age of infants was 19.5 ± 5.74 months with a M:F ratio of 5.5:1. Half (50%) of the infants were rural dwellers, 90% belonged to low socio-economic class and 70% were malnourished. A history of chronic diarrhoea was reported in 13% and urinary tract infections in 5%. The anatomic location was bladder in 487 (46.9%), kidney in 246 (23.6%), ureter in 142 (13.6%), urethra in 2 (0.2%) and 161 (15.5%) were passed spontaneously. Overall frequency of compounds in stones showed ammonium acid urate (AAU) in 772 (74.37%), calcium oxalate (CaOx) in 410 (39.5%). Uric acid (UA) in 119 (11.46%), calcium phosphate apatite (CaP) in 96 (9.25%), magnesium ammonium phosphate (Struvite) in 45 (4.34%), cystine in 12 (1.16%) and xanthine in 40 (3.85%). Frequency of compounds was similar in genders. Infants of age 0-6 months had higher frequency of UA (28%), CaOx (50%) and low AAU (61%) as compared to 11, 39 and 75%, respectively, in 7-24 months (p < 0.049) (p < 0.002) (p < 0.001). Nucleus of stones showed pure AAU in 63 and 43% on the surface due to addition of CaOx, struvite and CaP. Our study has shown that AAU is a major component of stones in infants where the main risk factors are poverty, malnutrition, diarrheal diseases and dehydration.

Surgical outcomes of percutaneous nephrolithotomy in 3402 patients and results of stone analysis in 1559 patients.

OBJECTIVE: To report our experience of a series of percutaneous nephrolithotomy (PCNL) procedures in a single centre over 18 years in terms of patient and stone characteristics, indications, stone clearance and complications, along with the results of chemical analysis of stones in a subgroup. PATIENTS AND METHODS: We retrospectively analysed the outcomes of PCNL in 3402 patients, who underwent the procedure between 1997 and 2014, obtained from a prospectively maintained database. Data analysis included patients' age and sex, laboratory investigations, imaging, punctured calyx, duration of operation, volume of irrigation fluid, radiation exposure time, blood transfusion, complications and stone-free status at 1-month follow-up. For the present analysis, outcomes in relation to complications and success were divided in two eras, 1997-2005 and 2006-2014, to study the differences. RESULTS: Of the 3402 patients, 2501 (73.5%) were male and 901 (26.5%) were female, giving a male:female ratio of 2.8:1. Staghorn (partial or complete) calculi were found in 27.5% of patients, while 72.5% had non-staghorn calculi. Intracorporeal energy sources used for stone fragmentation included ultrasonography in 917 patients (26.9%), pneumatic lithoclast in 1820 (53.5%), holmium laser in 141 (4.1%) and Lithoclast® master in 524 (15.4%). In the majority of patients (97.4%) a 18-22-F nephrostomy tube was placed after the procedure, while 69 patients (2.03%) underwent tubeless PCNL. The volume of the irrigation fluid used ranged from 7 to 37 L, with a mean of 28.4 L. The stone-free rate after PCNL in the first era studied was 78%, vs 83.2% in the second era, as assessed by combination of ultrasonography and plain abdominal film of the kidney, ureter and bladder. The complication rate in the first era was 21.3% as compared with 10.3% in the second era, and this difference was statistically significant. Stone analysis showed pure stones in 41% and mixed stones in 58% of patients. The majority of stones consisted of calcium oxalate. CONCLUSIONS: This is the largest series of PCNL reported from any single centre in Pakistan, where there is a high prevalence of stone disease associated with infective and obstructive complications, including renal failure. PCNL as a treatment method offers an economic and effective option in the management of renal stone disease with acceptable stone clearance rates in a resource-constrained healthcare system.

Borderline Changes on Dysfunctional Renal Allograft Biopsies: Clinical Relevance in a Living Related Renal Transplant Setting.

OBJECTIVES: Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting. MATERIALS AND METHODS: The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria. RESULTS: Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment. CONCLUSIONS: The borderline cellular infiltrates on dysfunctional renal allograft biopsies signify evolving phases of acute cellular rejection. These infiltrates responded favorably to antirejection treatment in our setting.

Problems Associated With Access to Renal Replacement Therapy: Experience of the Sindh Institute of Urology and Transplantation.

OBJECTIVES: The prevalence of end-stage renal disease is increasing worldwide. It is also one of the main health problems in Pakistan. Currently, hemodialysis represents the main mode of treatment for patients with end-stage renal disease in this country. Despite 24-hour free dialysis at the Sindh Institute of Urology and Transplantation (Karachi, Pakistan), a significant number of patients do not turn up for regular dialysis or miss regular sessions of dialysis. We conducted this study to identify and highlight the factors leading to poor compliance with regular hemodialysis treatment despite free dialysis treatment offered at our center. MATERIALS AND METHODS: In 2014, 4565 patients with end-stage renal disease were registered at the Sindh Institute of Urology and Transplantation. Among these, 610 patients (13.4%) missed more than 2 sessions of dialysis and were included in the present study. Patients provided written informed consent before study participation. Data were collected from a questionnaire survey and analyzed by SPSS software (SPSS: An IBM Company, version 20.0, Chicago, IL, USA). RESULTS: Despite 24-hour dialysis facilities, the patient drop-out rate (779; 18%) was high. In addition, a significant minority of patients (610; 13.4%) was erratic in adherence to maintenance hemodialysis schedules, with > 2 missed appointments. The mean age of these 610 patients was 33.4 ± 7.4 years, and 345 patients (57%) were males. The main factors leading to poor compliance included cost of travel (33.2%), lack of affordable lodging and boarding facilities near dialysis center (30.9%), long distances from dialysis center (20.1%), and lack of family support (15.6%). CONCLUSIONS: This study shows that there is significant drop-out and poor compliance rates for regular dialysis despite free dialysis facilities.

Kidney Swap in Pakistan: Experience at the Sindh Institute of Urology and Transplantation.

Kidney paired exchange is an established method of overcoming incompatibility in donor-recipient pairs and expanding the living-donor pool. It is infrequently performed in developing countries. We report the first kidney paired exchange in Pakistan, successfully performed at our center. One donor-recipient pair consisted of a 38-year-old female recipient (blood type, B positive) and her 40-year-old husband (A positive) as the potential donor. The second pair consisted of a 30-year-old male recipient (A positive) and his 30-year-old wife (B positive) as the potential donor. The donors were exchanged with the recipients, and both pairs were antigen matched for human leukocyte antigen A and human leukocyte antigen DR. Luminex antibody screening was negative, as were the crossmatches for T and B cells and for IgG and IgM. The transplant procedures and recoveries proceeded uneventfully. The recipients are maintaining serum creatinine levels around 0.78 mg/dL and 0.90 mg/dL, 1 year after transplant. Kidney paired exchange is a relatively low-cost option for overcoming the barrier of incompatibility in a resource-constrained setting.

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection.

BACKGROUND: CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients. METHOD: A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS®) and MedCalc® statistical software. RESULTS: Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve's characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan-Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001). CONCLUSION: In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes.

Metabolic risk factors in pediatric stone formers: a report from an emerging economy.

The goal of this study was to investigate metabolic risk factors in pediatric stone formers in an emerging economy. A prospective, data collection enrolled 250 children age <1-15 years at our center. Risk factors were evaluated by gender and in age groups <1-5, 6-10 and 11-15 years. Patients were evaluated for demographics, blood and 24 h urine for calcium, magnesium, phosphate, uric acid, electrolytes and additional protein, citrate, ammonia and oxalate in urine. All reported values were two sided and statistical significance was considered at p value ≤0.05. The mean age at diagnosis was 7.50 ± 3.56 years with a male to female ratio of 1.84:1. A family history of urolithiasis was found in 41 (16.4 %), urinary tract infection in 18 (7 %) and chronic diarrhea in 75 (30 %). Hypercalcemia was seen in 37 (14.8 %), hyperuricemia in 23 (9.2 %) and hyperphosphatemia in 6 (2.4 %). Urinary metabolic abnormalities were identified in 248 (98 %) of the cases. Hypocitraturia was found in 207 (82.8 %), hyperoxaluria in 62 (26.4 %), hyperuricosuria in 82 (32.8 %), hypercalciuria in 51 (20.4 %), hyperphosphaturia in 46 (18.4 %), hyperammonuria in 10 (4 %), hypocalciuria in 82 (32.8 %), and hypovolemia in 73 (29.2 %). Risk factors were similar between genders except higher rates of hyponatriuria, hypophosphaturia, and hypocalciuria in females. Hyperuricosuria, hyponatriuria, and hypovolemia were highest in 1-5 years (52, 49, 49 %) as compared to (18, 21, 12 %) those in 11-15 years (p < 0.001), respectively. This study shows that careful metabolic analysis can identify risk factors in 98 % of the children where appropriate metaphylaxis can be undertaken both for treatment and prevention of recurrence.

From diamonds to black stone; myth to reality: Acute kidney injury with paraphenylene diamine poisoning.

AIM: We report here, a case series of patients with acute kidney injury (AKI) after ingestion of paraphenylene diamine (PPD) a derivative of analine. It is used as a colouring agent to dye hair, fur and plastic and in photographic films. METHODS: Subjects for the study reported here comprised a cohort of 100 patients coming to this institution with AKI following PPD poisoning. AKI was defined according to RIFLE criteria and PPD poisoning on the basis of history and presenting features. All patients had normal sized kidneys on ultrasonography and no previous co- morbidity. RESULTS: One hundred patients with AKI after PPD exposure were brought to this institute between May 2010 and February 2015. Among these, 56 were females, with mean age of 23.11 ± 7.94 years. Cause of AKI was toxic rhabdomyolysis as indicated by marked rise in muscle enzymes with mean lactate dehydrogenase and creatinine phosphokinase levels of 6665.22 ± 6272.04 and 194 486.66 ± 301 905.80, respectively. Hepatotoxicity with raised aspartate aminotransferase and alanine aminotransferase was a main feature of the studied population. Renal replacement was required in 97% of patients. Complete renal recovery was observed in 77 patients, while 16 died during the acute phase of illness. Respiratory failure and recurrent hyperkalaemia were the main causes of mortality. CONCLUSION: Easy availability and low cost of PPD has lead to a remarkable increase in the use of this substance, especially for suicidal purposes. Awareness of its effects among health professionals, as well as at a societal and government level, is needed at this time.

Experience at a stricture clinic in a developing country.

OBJECTIVE: To evaluate the experience of 37 years regarding etiology, complications and evolving practice of the management of stricture urethra patients at the Sindh Institute of Urology and Transplantation, Karachi. METHODS: The retrospective descriptive study included 1600 cases of stricture urethra admitted to the Urology Section of the institute from 1972 to 2009. Files of all patients were reviewed; age, gender, site of stricture, etiology, diagnostic methods, clinical symptoms and management, as well trends and patterns were noted. RESULTS: There were 1600 patients of whom 1595 (99.4%) were males and 5 (0.4%) were females with age ranging from 14-80 years. Pelvic fracture urethral disfraction defects (n = 655; 49.5%) and fall astride (n = 123; 9.2%) were the commonest causes. Of the total, 92 percent presented with retention of urine. In the first decade, rail-road and dilatation was the mainstay of treatment. In the second decade, rail-road, dilatation and direct visual internal urethrectomy were the mainstay, but in the last 5 years, urethroplasty replaced the old methods. CONCLUSION: Trauma is the main cause of stricture. Over the years, urethroplasty and direct visual internal urethrotomy are the mainstay of management. Stricture clinic plays an important role in the early diagnosis of complications of stricture urethra and in the rehabilitation of these patients.

A kidney transplantation model in a low-resource country: an experience from Pakistan.

Pakistan is a low-resource country with a population of 185 million where expenditure on health is 1.3% of the gross national product. The estimated incidence of end-stage renal disease (ESRD) is 100 per million of the population. The paucity and high costs of renal replacement therapy render more than 90% of the ESRD population disenfranchised from replacement therapy. Our center, which is a government sector organization, established as an integrated dialysis and living related renal transplant program in the 1980s, where all services were provided free of cost to all patients with life-long follow-up care including medications. The model was based on a concept of community/government partnership where the contributions to funds vary between 40% and 60% for each partner. The model has been self sustaining for 25 years, with an annual budget of $28 million in 2010. Presently, over 600 patients are dialyzed each day and each week, 7-10 patients have received live related transplants. The overall 1- and 5-year graft survival rate of 3150 transplants is 92% and 85%, respectively. Free dialysis and transplantation established our institute as a focus of transplantation in the country. This model therefore allowed the institute to have a vital role in the campaign against transplant tourism and in the promulgation of the transplant law. It shows that in low-resource countries, specialized centers in the government sector can, with community support, provide high-quality ESRD care to the disenfranchised population.

Holmium laser urethrotomy for treatment of traumatic stricture urethra: a review of 78 patients.

OBJECTIVE: To evaluate the efficacy and long-term results of laser urethrotomy as minimally invasive treatment for traumatic stricture urethra. METHODS: Between January 2006 and June 2008, 78 male patients were treated with Holmium Laser urethrotomy. 16 Fr urethroscope was used through which 600um laser fiber was introduced through side channel. Stricture was visualized and incised at 12 o'clock position with energy set at 1500-2000 MJ at pulse rate of 10-12. Two other incisions were given at 2 and 10 o'clock positions. Further ablation was done till 16Fr Foley's catheter was passed. Patients were followed in a stricture clinic. RESULTS: Patients age ranged from 15-73 years. All strictures were due to trauma, Road traffic accident in 40 (52%) post catheter trauma 4 (5%), fall as ride 27 (35%) and failed urethroplasty 7 (8%). Site of stricture was bulbar 57 (73%), bulbomembranous 16 (20%) and membranoprostatic 5 (2.5%). Length of stricture ranged from 0.8-2.5 cms. At 3 months follow-up, 60 (77%) patients remained catheter and symptoms free while 18 (23%) developed recurrence of stricture but at the end of 36 months follow-up success rate decreased to 47 (60%). Among those who developed re-strictures, 6 ( 7.6%) had 2nd sitting laser while 4 (5.1%) had urethroplasty, and others were on intermittent dilatation. Immediate complications were sepsis 10 (13%), extravasation 2 (4%), failed urethrotomy 2 (4%) and mild haematuria 3 (5.8%). Hospital stay ranged from day care to 3 days. CONCLUSION: Laser urethrotomy is minimally invasive and an effective treatment for short strictures in bulbarurethra. The recurrence rate is 40% in the long-term follow-up and is more commonly seen in completely obliterated strictures.

The outcome of extracorporeal shockwave lithotripsy for renal pelvic stone with and without JJ stent--a comparative study.

OBJECTIVE: To compare the outcome of Extra corporeal shockwave lithotripsy for a renal pelvic stone with and without JJ stent. METHODS: A comparative cross sectional study was carried out at Sindh Institute of Urology and Transplantation from January 2007 to January 2008. Eighty patients with renal pelvic stone measuring 2cm +/- 2mm were selected for treatment with Extra Corporeal Shockwave Lithotripsy (ESWL). All of these patients were adults with normal renal function and had unilateral renal stones with negative urine cultures. Patients with renal failure and children were excluded. They were divided into two groups of 40 each. Group A patients underwent ESWL without a JJ stent and in Group B a JJ stent was placed before ESWL. SLX F2 electromagnetic ESWL machine was used to impart shock waves. 3000 shockwaves were given in a session. Both the groups were compared for renal colic, steinstrasse, fever, lower urinary tract symptoms (LUTS) emergency room visits and hospital admissions, stone clearance, number of ESWL sessions, auxilliary procedures, (percutaneous nephrostomy or ureterorenoscopy) and cost. RESULTS: Ureteric colic occurred in 13 (32.5%) patients in group A and in 3 (7.5%) patient in group B. Steinstrasse developed in 4 (10%) patients with out JJ stent and in 3 (7.5%) patients with JJ stent. Fever was encountered in 1 (2.5%) patient in group A and in 3 (7.5%) patient in group B. Mean emergency room visits were 2.1 per patient in group A and 0.7 per patient in group B. Stone clearance occurred in 33 (82.5%) patients in group A and 31 (77.5%) in group B. In group B lower urinary tract symptoms were found in 50% versus 20% in group A. Auxillary procedure was performed in one (2.5%) patient each in both groups. CONCLUSION: Pre ESWL JJ stenting for a 2 cm +/- 2 mm renal stone was not beneficial in terms of steinstrasse, fever, stone clearance and number of ESWL sessions. However ureteric colic was significantly less in the stented group. Lower urinary tract symptoms (LUTS) was also significantly high in the patients having a JJ stent. The cost of the treatment doubled in the stented group which is an important factor in our country. JJ stenting does not prove to be a cost effective procedure when compared to the reduction in complications.

Commercial transplants in local Pakistanis from vended kidneys: a socio-economic and outcome study.

Donor shortage and absence of transplant law lead to unrelated commercial transplants in Pakistan. We report the socio-economic and outcome parameters of 126 local recipients of unrelated kidney vendor transplants presenting to our institute between 1997 and 2007. Their outcome was compared with 180 recipients of living-related donor transplants matched for age, gender and transplant duration as controls. Age of commercial recipients was 35.63 +/- 11.57 years with an M:F ratio of 2.4:1. Majority (92%) were transplanted in northern Pakistan paying US$7271 +/- 2198. All were educated with 50% being graduates or above and rich earning a monthly salary of US$517 +/- 518 with 44% earning >US$500. Comparison of commercial recipients with controls showed high comorbidities 35 (28%) vs. 14 (8%) (P = 0.0001) with diabetes, hepatitis-C and cardiovascular diseases. Donor age was 29.97 +/- 6.16 vs. 32.63 +/- 9.3 years (P = 0.035). Biologic agents induction in 101 (80%) vs. 14 (8%) (P = 0.0001), acute rejections in 42 (33%) vs. 31 (17%) (P = 0.005), 1-year creatinine 1.84 +/- 1.28 vs. 1.27 +/- 0.4 mg/dl (P = 0.0001), surgical complications 28 (22%) vs. 14 (8%) (P = 0.001), tuberculosis 14 (11%) vs. 6 (6%) (P = 0.007), acute hepatitis 20 (16%) vs. 3 (2%) (P = 0.0001), cytomegalovirus 33 (26%) vs. 21 (11%) (P = 0.001) and recurrent urinary tract infection 35 (28%) vs. 30 (16%) (P = 0.034). Overall 1- and 5-year graft survival was 86% and 45% vs. 94% and 80%, respectively (P = 0.00001). Total deaths were 34 (27%) vs. 12 (6.0%) (P = 0.001). In conclusion, recipients of the vended kidneys are poor candidates, educated, rich and often self-selecting. Their outcome is poor, which will leave them poorer still and back to dialysis if not death.