Rosai Dorfman Disease With Extensive Bony Involvement- A Diagnostic Dilemma.

Previously classified as Non Langerhan cell histiocytosis by the Working Group of Histiocytic Society in 1987 Rosai Dorfman Destombes disease was first described by Destombes in 1965 and later in 1969 by Rosai and Dorfman as a rare histiocytic disorder with sinus histiocytosis and massive lymphadenopathy. They exist in both nodal and extranodal forms. Immunohistochemistry is an essential part of diagnosis to differentiate between Langerhans cell histiocytosis and another malignant histiocytosis. Some overlap has also been reported with IgG4-related diseases. We hereby reflect upon a patient who presented to our facility with pyrexia of unknown origin, the challenges faced to reach a diagnosis and the management offered.

Challenges in Diagnosis and Management of Glomerular Disease in Resource-Limited Settings.

Introduction: Glomerular diseases are the leading drivers of nondiabetic chronic kidney disease disability-adjusted life years in resource-limited countries. Proper diagnosis and treatment relies on resources including kidney biopsy, ancillary testing, and access to evidence-based therapies. Methods: We conducted a cross-sectional internet-based survey cascaded through society mailing lists among nephrologists in countries of Asia, Africa, and Eastern Europe. We collected the data on respondent demographics, their ability to perform and appropriately interpret a kidney biopsy, and their access to complementary investigations and treatment practices. Results: A total of 298 kidney care specialists from 33 countries (53.3% from Asia and 44.6% from Africa; 64% from academic or university hospitals) participated in the survey. Of these specialists, 85% performed kidney biopsy. About 61% of the respondents could not obtain a kidney biopsy in more than 50% of patients with suspected glomerular disease. About 43% of the respondents from Africa had access to only light microscopy. Overall, the inability to undertake and fully evaluate a biopsy and perform ancillary investigations were more profound in Africa than in Asia. Overall, 59% of participants reported that more than 75% of their patients meet the cost of diagnosis and treatment by out-of-pocket payments. Empirical use of immunosuppression was higher in Africa than in Asia. The main barriers for diagnosis and treatment included delayed presentation, incomplete diagnostic work-up, and high cost of treatment. Conclusion: Major system-level barriers impede the implementation of guideline-driven approaches for diagnosis and treatment of patients with glomerular disease in resource-limited countries.

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in South Asia.

Information about disease burden and the available infrastructure and workforce to care for patients with kidney disease was collected for the second edition of the International Society of Nephrology Global Kidney Health Atlas. This paper presents findings for the 8 countries in the South Asia region. The World Bank categorizes Afghanistan and Nepal as low-income; Bangladesh, Bhutan, India, and Pakistan as lower-middle-income; and Sri Lanka and the Maldives as upper-middle-income countries. The prevalence of chronic kidney disease (CKD) in South Asia ranged from 5.01% to 13.24%. Long-term hemodialysis and long-term peritoneal dialysis are available in all countries, but Afghanistan lacks peritoneal dialysis services. Kidney transplantation was available in all countries except Bhutan and Maldives. Hemodialysis was the dominant modality of long-term dialysis, peritoneal dialysis was more expensive than hemodialysis, and kidney transplantation overwhelmingly depended on living donors. Bhutan provided public funding for kidney replacement therapy (dialysis and transplantation); Sri Lanka, India, Pakistan, and Bangladesh had variable funding mechanisms; and Afghanistan relied solely on out-of-pocket expenditure. There were shortages of health care personnel across the entire region. Reporting was variable: Afghanistan and Sri Lanka have dialysis registries but publish no reports, whereas Bangladesh has a transplant registry. South Asia has a large, but poorly documented burden of CKD. Diabetes and hypertension are the major causes of CKD throughout the region with a higher prevalence of infectious causes in Afghanistan and a high burden of CKD of an unknown cause in Sri Lanka and parts of India. The extent and quality of care delivery is suboptimal and variable. Sustainable strategies need to be developed to address the growing burden of CKD in the region.

Catastrophic antiphospholipid antibody syndrome as a first manifestation of primary antiphospholipid antibody syndrome in a middle-aged man.

Catastrophic antiphospholipid antibody syndrome (CAPS) is a severe form of antiphospholipid antibody syndrome (APS) that sometimes represents the first manifestation of the later syndrome. The clinical manifestations of CAPS are relatively non-specific. Hence, the diagnosis may be delayed, resulting in high mortality. We herein present a case of a 40-year-old male who presented with rapid-onset renal failure, gangrene of finger and toe tips and hematological abnormalities with no underlying secondary cause for this complication. The symptoms were precipitated by febrile illness of short duration. A provisional diagnosis of CAPS was made and treatment instituted. With timely diagnosis and intervention, both the life of the patient and kidney function were salvaged. A high index of suspicion for CAPS is important as early treatment can be lifesaving.

Posttransplant diabetes mellitus among live-related kidney transplant recipients: Sindh Institute of Urology and Transplantation experience.

This cross-sectional study conducted at Sindh Institute of Urology and Transplantation, Karachi, Pakistan aimed to determine the frequency and risk factors of posttransplant diabetes mellitus (PTDM) among live-related kidney transplant recipients and their short-term prognosis and included renal transplant recipients (nondiabetic before transplant) of either gender, aged 18-60 years with transplant duration two to six months. Patients with two reading of fasting plasma glucose ≥126 mg/dL were labeled as diabetic. A total of 191 patients (154 males and 37 females) with the age between 18 to 60 years (31.5 ± 9.33 years) were included and 30 patients (15.8%) including 23 males and seven females had PTDM. Age of the patients between 26 and 35 years, previous hepatitis C virus (HCV) infection/antiviral therapy, and Tacrolimus as maintenance immunosuppression were found to be more frequent among those with PTDM. After six months of follow-up, the serum creatinine of patients with PTDM was significantly higher than that of those without PTDM (1.15 ± 0.28 vs. 1.01 ± 0.16, P ≤0.0121); however at one year follow up, there was no significant difference between the serum creatinine of both groups (1.28 ± 0.38 vs. 1.37 ± 0.59, P = 0.332). PTDM is an important metabolic derangement affecting a number of kidney transplant recipients. Its risk factors are previous HCV infection, tacrolimus as immunosuppression and young age. It can have an adverse effect on graft function and survival. Therefore, long-term follow-up is warranted to optimize the graft function and patient survival.

Acute tubulointerstitial nephritis/drug induced acute kidney injury; an experience from a single center in Pakistan.

INTRODUCTION: There is no information in literature specifically on the prevalence and clinicopathological characteristics of acute tubulointerstitial nephritis/drug induced acute kidney injury (AKI) from Pakistan. OBJECTIVES: We aim to report a series of cases from patients developing AKI after exposure to some medications or finding of interstitial nephritis on histopathology. PATIENTS AND METHODS: This is an observational study of patients identified as having AKI after exposure to medications. AKI was defined according to RIFLE criteria and all patients fell from risk to loss category on arrival. On ultrasonography, all patients had normal size non-obstructed kidneys. Renal biopsy findings were consistent with tubule interstitial nephritis. RESULTS: Mean age of patients was 36.41 ± 17.40 years. Among total of 155, 80 were male and 75 female. Regarding drugs, most common was exposure to aminoglycoside in 34 (22%) followed by use of non-steroidal anti-inflammatory analgesics in 28, contrast induced agents in 11. Renal biopsy was performed in 58 patients. In half of these, insulting agent was not known and in rest either multiple medications were ingested or there was denial to substance use or recovery was delayed despite discontinuation of responsible medication. Renal replacement therapy was required on arrival in 119/155 (hemodialysis = 115, peritoneal dialysis = 4) cases. Complete renal recovery was observed in 71%, while 7.7% expired during acute phase, partial renal recovery was seen in 15% and 5% disappeared after first discharge from the hospital. CONCLUSION: Tubulointerstitial nephritis may occur with many drugs of common use. Early and intensive efforts must be made to consider and then timely correct the injury to the kidney.

Long-term Safety of Living Kidney Donation in an Emerging Economy.

BACKGROUND: Long-term follow-up and management of donors was undertaken in a specialist kidney transplant unit in Pakistan to identify risk and prevent adverse outcomes in living related kidney donors. METHODS: In an observation cohort study between 1985 and 2012, 3748 donors were offered free medical follow-up and treatment 6 to 12 months after donation and annually thereafter. Each visit included history, physical examination, blood tests for renal, lipid, glucose profiles, and 24-hour urine for proteinuria and creatinine clearance. Preventive intervention was undertaken for new onset clinical conditions. Donor outcomes were compared with 90 nondonor healthy siblings matched for age, sex, and body mass index. RESULTS: Of the 3748 donors, 2696 (72%) were in regular yearly follow-up for up to 27 years (median, 5.6; interquartile range, 7.9). Eleven (0.4%) died 4 to 22 years after donation with all-cause mortality of 4.0/10 000 person years. Six (0.2%) developed end-stage renal disease 5 to 17 years after donation, (2.7/10 000 person years). Proteinuria greater than 1000 mg/24 hours developed in 28 patients (1%), hypertension in 371 patients (13.7%), and diabetes in 95 patients (3.6%). Therapeutic intervention-controlled protein was less than 1000 mg/24 hours, blood pressure was below 140/90 mm Hg, and glycemic control in 85% up to 15 years after onset. Creatinine clearance fell from 109.8 ± 22.3 mL/min per 1.73 m predonation to 78 ± 17 at 1 year, 84 ± 19 at 5 years, and 70 ± 20 at 25 years. Comparison of 90 nondonor sibling and donor pairs showed significantly higher fasting glucose and hypertension in nondonors. CONCLUSIONS: Long-term follow-up of donors has demonstrated end-stage renal disease in 0.6% at 25 years. Regular follow-up identified new onset of disease and allowed interventions that may have prevented adverse outcomes.

Spectrum of glomerular diseases causing acute kidney injury; 25 years experience from a single center.

INTRODUCTION: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. OBJECTIVES: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. PATIENTS AND METHODS: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. RESULTS: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. CONCLUSION: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome.

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.

Factors predicting the outcome of acute renal failure in pregnancy.

OBJECTIVE: To determine the factors predicting renal outcome in patients developing acute renal failure in pregnancy. STUDY DESIGN: Descriptive cohort study. PLACE AND DURATION OF STUDY: Study was conducted at Nephrology Unit of Sindh Institute of Urology and Transplantation, Karachi, from October 2006 to March 2007. METHODOLOGY: Patients with acute renal failure due to complications of pregnancy, with normal size of both the kidneys on ultrasound were enrolled, and followed for a period of 60 days or until recovery of renal function. Patient's age and parity, presence of antenatal care, type of complication of pregnancy, foetal outcome and duration of oliguria were compared between patients who remained dialysis dependent and those who recovered renal function. Chi-square/Fisher's exact test and student's t-test, were used for determining the association of categorical and continuous variables with dialysis dependency. RESULTS: The mean age was 29+/-6 years. Most patients came from rural areas of interior Sindh. Sixty eight percent did not have antenatal checkups. Antepartum haemorrhage (p=0.002) and prolonged duration of oliguria (35+/-15.7 days, p= < 0.001) were associated with dialysis dependency, which was observed in 50% of the study group. CONCLUSION: Ante-partum haemorrhage and prolonged oliguria were strong predictors of irreversible renal failure. This highlights the need for early recognition and referral, and the importance of trained birth attendants and antenatal care.

Range for normal body temperature in hemodialysis patients and its comparison with that of healthy individuals.

BACKGROUND/AIMS: Patients with chronic kidney disease undergoing hemodialysis have an altered homeostasis leading to altered body temperatures. We aimed to determine the range for normal body temperature in hemodialysis patients and compared it to healthy individuals. Also, we determined how much axillary temperatures differed from oral temperatures in both groups and whether axillary temperature is affected by the presence of an arteriovenous fistula (AVF) in hemodialysis patients. METHODS: Oral and axillary (left & right) temperatures were recorded using an ordinary mercury-in-glass thermometer in 400 subjects (200 hemodialysis patients, 200 healthy individuals) at the Sindh Institute of Urology and Transplantation from mid-May to mid-June 2006. Comparisons were made between the temperatures of both groups. RESULTS: Mean oral temperature in hemodialysis patients was higher than in healthy individuals [98.7 degrees F (37 degrees C) vs. 98.4 degrees F (36.8 degrees C); p < 0.001], as was the mean average axillary temperature [97.7 degrees F (36.5 degrees C) vs. 97.5 degrees F (36.3 degrees C); p = 0.02] and mean left axillary temperature [97.9 degrees F (36.6 degrees C) vs. 97.6 degrees F (36.4 degrees C); p < 0.001]. The fistula arm had higher axillary temperature in 77 (44%) hemodialysis patients. The difference between oral and axillary temperatures varied widely, making it impossible to obtain an accurate correction factor in both groups. CONCLUSION: Hemodialysis patients have higher normal body temperatures than healthy individuals. Axillary temperatures require cautious interpretation. In hemodialysis patients, the non-fistula arm should be preferred for recording axillary temperatures, as the presence of AVF may cause discrepancies in temperature measurements.

Use of isoniazid chemoprophylaxis in renal transplant recipients.

BACKGROUND: The use of isoniazid (INH) as chemoprophylaxis for tuberculosis (TB) in renal transplant recipients has not been widely studied or reported from a country where TB is endemic. We are reporting here the results of the largest ever-reported randomized, prospective study of the use of INH in renal transplant recipients. METHODS: Four hundred consecutive live related renal transplant recipients between April 2001 and September 2004, from this single center, were randomized to receive or not receive INH for 1 year after transplantation. RESULTS: There were 12 dropouts. Of the remaining 388, 181 recipients received INH for 1 year post-transplant and 207 did not. The primary disease, comorbidities, HLA (human leucocyte antigen) match, immunosuppression, episodes of rejection, the use of anti-rejection agents, a past history of TB in the donor, the recipients and in family members living in same house and a history of TB in the family were factors compared in the two groups. The only significant difference between the two groups was that there was an increased family history of TB in recipients who received INH (P = 0.01). One recipient from the INH group and 16 recipients from the non-INH group developed TB (P = 0.0003). Discontinuation of INH for hepatotoxicity was not required in any patient. CONCLUSION: These results provide evidence that the use of INH following renal transplantation should be considered mandatory in geographical areas where the prevalence of TB is high. Furthermore, these results have important implication in patients from such areas who are immunosuppressed following other kinds of transplantation and for those who are immunocompromised for any other reason.

Prevalence of metabolic syndrome in renal transplant recipients--a single centre experience.

OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) in renal transplant recipients (RTR) using the modified Asian National Cholesterol Education Programme-Adult Treatment Panel III (NCEP-ATP III) criteria. METHODS: A cross-sectional study was conducted on 200 RTRs between January 2008-August 2008. All were more than six months post transplant and above 18 years of age. Subjects with pre-transplant diabetes or New Onset Diabetes Mellitus after renal transplantation, with overt infections, dyslipidaemia or on lipid lowering medication and taking immunosuppressive drugs of the target organ inhibitor group as rapamycin, were excluded. The prevalence of MS was determined using the (NCEP-ATP III) criteria modified for Asians which includes waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting blood glucose. RESULTS: Of the 200 recipients studied, 87 (43.5%) had MS. There were 58 (39.4%) males and 29 (54.7%) females which shows female predominance. The mean age of the MS group was more then that of the non MS group (p < 0.0001). Hypertension and New Onset Diabetes Mellitus were prevalent more in MS group (p < 0.001 and p < 0.0001 respectively). Mean serum creatinine was higher in MS group but there was no significant difference. The prevalence of MS was 4.5% in the first twelve months, with a rise in this figure to 41.3% between one to five years after transplantation. CONCLUSION: There is a high prevalence of MS in Renal Transplant Recipients specifically after one year of transplantation.

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.

Living kidney donor follow-up in a dedicated clinic.

BACKGROUND: Long-term effects of uninephrectomy for kidney donation are of particular interest in the currently increasing practice of living-donor transplantation. We have retrospectively analyzed the general health status and renal and cardiovascular consequences of living-related kidney donation. METHODS: Data of living-related kidney donors who were regularly followed up in a dedicated clinic at the Sindh Institute of Urology and Transplantation between July 2000 and January 2004 was retrieved. They had donated their kidneys from 1986 onward. Data on weight, blood pressure, creatinine clearance, level of proteinuria, and new onset diabetes mellitus were analyzed. RESULTS: Seven hundred and thirty-six donors with a mean age of 36+/-10.9 years (M:F 1.1:1) were evaluated. With a mean postnephrectomy duration of 3+/-3.2 years (range 6 months-18 years), the creatinine clearance fell to 87% of prenephrectomy values, and 49 (6.7%) had a creatinine clearance of less than 60 mL/ min. Hypertension developed in 76 (10.3%) donors, and 179 (24.3%) had proteinuria exceeding 150 mg/24 hr. Overweight (27.8%) and obese subjects (11.5%) had a higher prevalence of hypertension and new onset diabetes mellitus. One donor developed end-stage renal failure. CONCLUSION: Donor nephrectomy has minimal adverse effects on overall health status. Regular donor follow-up identifies at-risk populations and potentially modifiable factors.

Outcome in severe acute renal failure associated with malaria.

BACKGROUND: Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This study reports its occurrence with a serious complication, acute renal failure (ARF), at a Third World tertiary care centre. METHODS: All registered patients with ARF who had history and clinical findings suggestive of malaria and had malarial parasites on peripheral blood smears were included in this study. The data on their modes of presentation, management and outcome have been analysed. RESULTS: Between January 1990 and December 1999, a total of 2098 patients with ARF were seen at the centre. Of these, 124 (5.9%) developed ARF due to malaria (falciparum in 121 and vivax in three). The male:female ratio was 4:1 and 84 (68%) patients were oligo- or anuric on presentation. Mean serum creatinine on admission was 9.43 +/- 5.39 mg/dl and 99 (79.8%) patients required renal replacement therapy. Of the cohort, 32 (25.8%) died, most within 48 h of admission. Age, oliguria, central nervous system involvement and presence of disseminated intravascular coagulopathy emerged as bad prognostic factors in simple univariate analysis. Of the survivors, 77 (62%) had complete recovery of renal function, while 15 (12%) were progressing towards recovery when lost to follow-up. The number of dialysis sessions did not differ significantly between the oliguric and non-oliguric groups. CONCLUSIONS: In patients who do not succumb early to ARF of severe malaria, treatment with antimalarials and dialysis brings about recovery of renal function.

Renal transplantation in developing countries.

Healthcare in developing countries less funded than developed nations (0.8 to 4% vs. 10 to 15%, respectively), and must contend against approximately 1/3 of the population living below the poverty line ($1US/day), poor literacy (58% males/29% females), and less access to potable water and basic sanitation. Cultural and societal constraints combine with these economic obstacles to translate into poor transplantation activity. Donor shortage is a universal problem. Paid donation comprises 50% of all transplants in Pakistan. Post-transplant infections are a major problem in developing countries, with 15% developing tuberculosis, 30% cytomegalovirus, and nearly 50% bacterial infections. The solutions to these problems may seem simplistic: alleviate poverty, educate the general population, and expand the transplant programs in public sector hospitals where commerce is less likely to play a major role. The SIUT model of funding in a community-government partnership has increased the number of transplantations and patient and organ survival substantially. Over the last 15 years, it has operated by complete financial transparency, public audit and accountability. The scheme has proven effective and currently 110 transplants/year are performed, with free after care and immunosuppressive drugs. Confidence has been built in the community, with strong donations of money, equipment and medicines. We believe this model could be sustained in other developing nations.