Percutaneous renal biopsy results: a retrospective analysis of 511 consecutive cases.

To determine the patterns of the prevalent glomerulonephritis (GN) in our region, we studied the results of 511 consecutive renal biopsies performed on patients with proteinuria, hematuria and mild to moderate renal impairment at the Aga Khan University Hospital during a period of 18 years from January 1990 to December 2008. Primary glomerular disease accounted for two-thirds of the glomerular diseases, which in turn constituted 49% of all renal biopsies. The most common histological lesion was membranoproliferative disease (28%). Membranous GN was the second most common lesion (19%), followed by minimal change disease (16%) and focal segmental GN (11%). Secondary glomerular disease comprised 30% of glomerular diseases (21% of all the renal biopsies), with lupus nephritis forming the most common lesion (34%) followed by amyloidosis (22%), diabetic nephropathy (10%), Wagener's granulomatosus and post-infectious GN (9% each). Tubulointerstitial diseases accounted for 16% of all the renal biopsies. We conclude that there exists a wide variability in the different categories of primary and secondary glomerular diseases in our region as compared with different parts of the world. Future studies should be directed to analyze the causes for these variations.

Biochemical nutritional parameters and their impact on hemodialysis efficiency.

To determine the nutritional status of chronic hemodialysis (HD) patients and the association of changes in serum albumin levels, C-reactive protein (CRP), low density lipoprotein (LDL) cholesterol and body mass index (BMI) as indicators of nutritional status with the urea reduction ratio (URR) during dialysis, we studied 201 chronic HD patients (97 males and the mean age was 51 +/- 15 years). Diabetes was the cause of chronic kidney disease (CKD) in 34% of the patients, hypertension in 57%, chronic glomerulonephritis in 12%, and obstructive uropathy in 10%. BMI less than 18.5 (under weight) was found in 17% of patients, more 18.5 but less than 25 (normal) in 56%, more than 25 but less than 30 (overweight) in 21%, and more than 30 (obese) in 6%. The laboratory investigations revealed hypercalcemia in 62% of the patients (15 patients were found to have tertiary hyperparathyroidism), total cholesterol less than 100 mg/dL in 6% (mean 152 +/- 37.5 mg/dL), and URR of less than 60% in 12% of patients and greater than 60 but less than 65% in 33%. Hypoalbuminemia was associated with poor URR (P < 0.05), whereas no statistically significant correlation was found between URR and iPTH, LDL cholesterol, CRP and body mass index. We conclude that poor nutritional status was detected among a significant number of our patients with poor dietary education. Increased risk of malnutrition was significantly associated with older age and inadequate dialysis dose. Hypoalbuminemia was the single most important factor associated with poor URR.

Survival analysis and prognostic indicators of systemic lupus erythematosus in Pakistani patients.

To aim of this study is to analyse the survival rate and prognostic indicators of systemic lupus erythematosus (SLE) in Pakistani population. A total of 198 patients with SLE diagnosed between 1992 and 2005 were reviewed retrospectively. Clinical features at presentation, subsequent evolving features, autoantibody profile, damage scores and mortality data were obtained. Prognostic factors for survival were studied by statistical analysis. Of 198 SLE patients studied, 174 were women and 24 were men. The women to men ratio was 7.2:1. Mean age at presentation was 31 years (range 14-76). Mean duration of symptoms before diagnosis was 2.8 years. Mean duration of follow-up was 34.21 months (+/-33.69). Mean disease duration was 15.6 years. At diagnosis, arthritis, malar rash, oral ulcers and alopecia were the commonest features. During the follow-up, the prevalence of nephritis, arthritis, neurological and hematological disease increased significantly. About 76% (n = 151) of the patients had organ damage at the time of data analysis, and renal disease was the commonest cause. Univariate analysis revealed that renal disease (P = 0.000), seizures (P = 0.048), pleural involvement (P = 0.019), alopecia (P = 0.000) and discoid lesions (P = 0.005) were predictors for damage. Multivariate model, however, revealed that only renal disease was independent risk factor for damage (P = 0.002). During the study period, 47 patients (24%) died (five due to disease-related complications and rest as a result of infections). The 3-, 5-, 10-, 15- and 20-year survival rates of our cohort were 99, 80, 77, 75 and 75%, respectively. Cox regression analysis revealed that renal involvement (P = 0.002) and infections (P = 0.004) were independent risk factors for mortality. The survival of our Pakistani SLE patients was significantly lower compared to that of the Caucasian series reported in last decade. Nephritis not only contributes to organ damage but also acts a major determinant for survival. Infection remains the commonest cause of death. Renal involvement and infections are independent risk factors for mortality. Judicious use of immunosuppressive agents is necessary to improve the short-term survival of lupus patients.

Clinical presentation and outcome of autosomal dominant polycystic kidney disease in Pakistan: a single center experience.

OBJECTIVE: To delineate clinical presentation and outcome of Autosomal Dominant Polycystic Kidney Disease (ADPKD) in terms of need for renal replacement therapy of kidney transplantation in Pakistani patients. METHODS: Patients with ADPKD were identified using strict clinical criteria. Medical charts were evaluated retrospectively for initial presenting complaints, co-morbids, family history of ADPKD, any palpable mass on abdominal examination, cardiac examination for any abnormal finding and use of any anti-hypertensive drugs. Laboratory parameters were assessed. Chi square and Logistic regression analyses at 95% CI were used for statistical significance. A p value of less 0.05 was considered statistically significant. RESULTS: A total of 56 patients fulfilled our criteria of ADPKD. There were 40 (71.4%) males and 16 (28.6%) females in our study. The mean age at the time of diagnosis of ADPKD was 47.0 +/- 14.5 years. Mean follow up period for all patients was 7.6 +/- 4.2 years. Most common form of presentation was hypertension in 38 (67.9%) patients. Kidneys were palpable in 33 (58.9%), liver in 16 (28.6%) and spleen in 6 patients (10.7%). Microscopic haematuria was observed in 38 (67.8%) patients while gross haematuria was present in 10 (17.9%) patients. The murmur of mitral valve prolapse was found in 10 patients on clinical examination which was later confirmed on transthoracic echocardiography (TEE). On MRI/MRA 2 (3.6%) patients each had berry aneurysm and AV malformations. Three patients (5.4%) received renal transplant and 19 (33.9%) patients were dialysis dependent at the end of study. A total 11 (20%) were lost to follow up. Two patients (3.5%) died during six years follow up. Male sex and uncontrolled hypertension were most important predictors of poor prognosis (p < 0.03 and < 0.048 respectively). CONCLUSION: Pre-symptomatic patients with ADPKD should be monitored with blood pressure measurements and assessment of their renal function. The advantages of such monitoring include the ability to prevent or control infection and hypertension, to identify potential kidney donors from among the family, to offer advice on marriage and childbearing, and to provide prenatal diagnosis.

Etiology of acute renal failure in a tertiary center.

Acute renal failure (ARF) occurs commonly in developing countries. Our aim was to assess the etiologies and outcomes of ARF in a tertiary care hospital in Pakistan and compare them with data from developed and developing countries. All patients admitted to the Aga Khan University Hospital, Karachi from January 1991 to December 2000 fulfilling the criteria of acute renal failure were reviewed retrospectively. Acute renal failure for the purpose of this study was defined as persistent elevation of serum creatinine to above 2 mg/dL (177 umol/L) on two consecutive occasions despite correction of any abnormal hemodynamic or mechanical factors. We studied 898 patients fulfilling the criteria of ARF, 61% (551) were males, and the mean age was 53% +/- 17.6 (range 15-91) years. Medical causes accounted for (88%) of ARF cases and surgical causes for (11%). Majority of the patients had pre-renal ARF, and 5% had drug related ARF. The base line creatinine was 1.9 +/- 1.8 mg/dL, while 27% of the patients had pre-existing chronic kidney disease. The mean rise in creatinine was 7.18 +/- 3.8 mg/dL. We conclude that ARF resulted from pre-renal etiologies in majority of the patients and early recognition and management may improve the prognosis of these potentially preventable causes.

Association of angiotensin-converting enzyme gene dimorphisms with severity of lupus disease.

Angiotensin-converting enzyme (ACE) plays an important role in the development of systemic lupus erythematosus (SLE) because its end-product, angiotensin II, plays an integral role in the regulatory system responsible for endothelial control and vascular tone, systems that are commonly affected in patients with SLE. Additionally, ACE inhibitors have been shown to retard the progression of SLE and lupus nephritis. Our goal was to investigate whether ACE gene polymorphisms are associated with increasing severity of SLE. We genotyped 39 SLE patients of varying disease severity from a homogenous Asian population and 79 control subjects for ACE I/D and 2350 G > A dimorphisms. All patients met the American College of Rheumatology (ACR) criteria for SLE and their disease severity was measured using Systemic Lupus Activity Measure (SLAM). The "A" allele was found to be associated with increase in severity of SLE with the AA genotype present only in severe disease. No association with SLE in general, compared to healthy subjects, was found with either dimorphism. We also examined the transmission of haplotypes as defined by these polymorphisms. The D and A alleles were found in strong linkage disequilibrium especially in severe SLE. The DA-haplotype was more frequent in severe SLE, than mild to moderate disease. Our findings suggest that DNA sequence variation in the ACE gene influences disease progression and severity of SLE.

Pre-operative renal function and selective renal vein renin levels as markers of favourable outcome in renovascular hypertension.

OBJECTIVE: To evaluate factors that affect outcome following revascularization in patients with renovascular hypertension. METHODS: This study was conducted at the Aga Khan University Hospital. It included all the patients diagnosed to have Renovascular hypertension confirmed by renal angiography between July 1996 to September 2000. Using ANOVA (Analysis of variance) and paired-sample t-test, several preoperative factors were evaluated for their ability to predict postoperative improvement of blood pressure and renal function. For descriptive purpose patients were divided into cured, improved and failure groups. RESULTS: Of the total 15 patients, 9 were males and 6 were females. Before the surgical procedure, 13 patients were on 3 or more antihypertensive drugs. Eleven patients received vein grafts, three patients had PTFE (polytetraflouroethyline) grafts while one patient underwent angioplasty and stenting. The patients had a median follow-up period of nine months with a range of 2 to 84 months. Five were completely cured, as they became normotensive without antihypertensive therapy after operation, whereas four showed marked improvement in BP control postoperatively, requiring two antihypertensive drugs. Six patients showed no improvement requiring 3 or more drugs. Extended cure or improvement of renovascular hypertension was achieved in nine patients. Normal preoperative serum creatinine level, high preoperative unstimulated peripheral renin levels and renal vein renin ratio of at least 1.75:1 were the most significant predictive factors for favorable outcome. CONCLUSION: This study confirms the long term effectiveness and safety of renovascular reconstruction in the relief of severe hypertension. The results further suggest that normal preoperative renal function, high renal vein renin ratio and high preoperative unstimulated peripheral renin levels are associated with the most favourable postoperative outcome (p <0.01). Preoperative severity and duration of hypertension and degree of disparity in kidney sizes do not affect the overall results in terms of postoperative improvement in renal function and blood pressure control (p=0.734).

Do clinical manifestations of Systemic Lupus Erythematosus in Pakistan correlate with rest of Asia?

OBJECTIVE: Systemic Lupus Erythematosus (SLE) is known to be different among people with different racial, geographical and socio-economic back grounds. Asia has diverse ethnic groups broadly, Orientals in the East and Southeast Asia, Indians in South Asia and Arabs in the Middle East. These regions differ significantly from the Caucasians with reference to SLE. The purpose of this study was, therefore, to delineate the clinical pattern and disease course in Pakistani patients with SLE and compare it with Asian data. METHODS: Patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association admitted at the Aga Khan University Hospital between 1986 and 2001 were studied by means of a retrospective review of their records. The results were compared with various studies in different regions of Asia. RESULTS: Demographically, it was seen that SLE is a disease predominantly of females in their third decade, which is generally consistent with Asian data. There was less cutaneous manifestations, arthritis, serositis, haematological and renal involvement compared to various regions in Asia. The neurological manifestations of SLE, however, place Pakistani patients in the middle of a spectrum between South Asians and other Asian races. CONCLUSION: This study has shown that the clinical characteristics of SLE patients in our country may be different to those of other Asian races. Although our population is similar to South Asians, but clinical manifestations of our SLE patients are considerably different, suggesting some unknown etiology. Further studies are required to confirm the above results and to find statistically sounder associations.

Ischemic monomelic neuropathy: a complication of vascular access procedure.

Ischemic monomelic neuropathy (IMN) is an infrequently recognized type of ischemic neuropathy produced by shunting of blood or due to acute noncompressive occlusion of the major proximal limb artery. Most reports about this complication appear in the neurology literature. IMN predominantly occurs in diabetic patients with evidence of peripheral neuropathy and atherosclerotic peripheral vascular disease. We report a case of ischemic monomelic neuropathy occurring in a patient with end stage diabetic nephropathy following PTFE (polytetrafluoroethylene) graft placement in proximal upper limb for chronic maintenance hemodialysis.

Renal involvement in systemic lupus erythematosus in Pakistan.

OBJECTIVE: To find the prevalence of lupus nephritis, delineate its clinical, immunological and therapeutic characteristics and compare them with the data worldwide. PATIENTS AND METHODS: Between 1985 and 2001, 198 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association (ARA) admitted to the hospital were studied by means of a retrospective review of their records. RESULTS: Renal involvement was found in 89 (45%) patients. Biopsy showed lupus nephritis in 42 patients; there were 9 male and 33 females. Mean age at initial presentation was 27 years and mean duration of follow-up was 2 .3 years. The histological types (WHO Classification) were mainly class. 4 (n = 27), class 3 (n = 7) and class 5 (n = 6). Immunoflourescence showed a predominantly granular pattern of IgG, IgA and C3. Renal manifestations included renal failure (50%), microscopic hematuria (67%), active urine sediment (22%), and proteinuria (74%). Proteinuria was nephrotic range in 45% patients. Treatment was with combinations of prednisolone and cyclophosphamide (n = 13), prednisolone and azathioprine (n = 27). 19 patients received high dose methyl prednisolone (1 gm/day for 3 days). There was no difference in mortality rate between prednisolone and cyclophosphamide and prednisolone and azathioprine treatment groups. The overall mortality rate was 17% (n = 7). Mortality was higher in WHO class 4 and 5 as compared to class 2 and 3 (p < 0.001). CONCLUSION: The prevalence of lupus nephritis in our population is an intermediate between Caucasians and other Asians. Certain clinical characteristics in our patients with lupus nephritis are different as compared to various other studies. Because of limited resources for treatment in developing countries, we believe that patients with lupus nephritis should be treated with improved ancillary medical therapies and more effective immunosuppressive regimens.

Clinico-laboratory findings in male lupus patients from a tertiary care hospital, Pakistan.

This study was conducted to delineate the clinical pattern of a cohort of Pakistani male patients with systemic lupus erythematosus (SLE). Clinical and laboratory data were collected of 24 male patients who were diagnosed with SLE and admitted to a tertiary care hospital between 1986 and 2001. Imaging and invasive studies (including aspirations and biopsies) were also recorded. Fourteen patients (58%) had renal involvement, with WHO class 4 and 5 comprising 89% of the cases. Eight patients (33%) had neurological involvement. Out of these 8 patients, 3 presented with psychosis (12.5%) and 4 (17%) with seizures. Twenty three patients (96%) had hematological involvement, 6 (25%) had serosal and 10 (41%) had articular involvement. Cutaneous lesions were noted in 10 (41%) patients. A majority of the patients were noncompliant and were lost to follow-up; therefore, ultimate outcome could not be clearly delineated. A high index of suspicion for SLE in males may permit early diagnosis and dictate the need for more aggressive therapy.

Systemic lupus erythematosus presenting as hemolytic uremic syndrome: a case report.

Associating systemic lupus erythematosus (SLE), with an initial presentation of hemolytic uremic syndrome (HUS) is rare. We report a case of 21-year old Afghani female admitted to our hospital with an initial complaint of high grade fever and diffuse maculopapular rash and swelling of lower limbs. Diagnosis of atypical HUS was established according to the clinical triad of HUS without a veriotoxin-producing organism in her stool and the pathological finding compatible to thrombotic microangiopathy. In addition, her symptoms fulfilled the 1982 revised criteria for the classification of SLE. After pulse methylprednisolone, cyclophosphamide and plasmapheresis therapies, her laboratory findings and general condition improved. Unfortunately she was lost to follow up as she decided to return back to Afghanistan.

Contrast nephropathy in high-risk patients undergoing coronary angiography and intervention.

OBJECTIVE: To determine the incidence of contrast nephropathy in high-risk patients undergoing coronary angiography and percutaneous coronary intervention (PCI), and to define the characteristics of this cohort. DESIGN: Discriptive study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi from January to December 2002. PATIENTS AND METHODS: One hundred and fifteen patients with serum creatinine greater than 1.4mg/dl who underwent coronary angiography or PCI were included. All patients received non-ionic contrast dye. Acute contrast nephropathy was defined as rise in serum creatinine of 0.5mg/dl within 48 hours following the index procedure. Means and standard deviations were calculated for continuous variables and frequencies for categorical variables. RESULTS: Mean age of patients was 62.3 years +/- 8.83. Mean pre-contrast creatinine was 1.9 +/- 0.9 mg/dl. Eleven (9.65%) patients developed contrast nephropathy. 4.4% of patients with serum creatinine < 2.0 developed contrast nephropathy compared to 42.9% of patients with creatinine > 4.0(p-value 0.001). 11.9% diabetic patients developed nephropathy compared to 6.3% of non-diabetics(p-value 0.355). 11.4% of hypertensive and 3.7% of non-hypertensive patients developed contrast-nephropathy (p-value 0.454). 12.9% of low dose group(<100 ml) and 5.7% of high dose group (>100 ml) developed nephropathy (p-value 0.188). Mean serum creatinine in low dose group was higher (3.0 mg/dl vs. 1.7 mg/dl). CONCLUSION: The incidence of contrast nephropathy in this study was similar to that reported in literature. Risk of CIN was found to be significantly proportional to the severity of baseline renal disease. Trends towards higher risk of CIN were seen in patients with diabetes and hypertension. Higher incidence of CIN in patients receiving low-dose contrast was confounded by higher baseline serum creatinine in that group.

Renovascular hypertension: factors affecting the outcome following surgical revascularisation.

This study was conducted at the Aga Khan University Hospital, Karachi, Pakistan to evaluate factors that affect outcome following revascularisation in patients with renovascular hypertension. We included all the patients diagnosed to have renovascular hypertension, confirmed by renal angiography, between July 1997 and September 2000. Of the total 15 patients, nine were males and six were females. Eleven patients received venous grafts, three received polytetraflouroethyline (PTFE) grafts while one patient underwent angioplasty and stenting. All were followed-up for a period of nine months (median) with the range from 2 to 84 months. A total of 33.3% of the study patients were completely cured, as they became normotensive without anti-hypertensive therapy after operation, while 27% showed marked improvement in blood pressure control post-operatively. Thus, extended cure or improvement of renovascular hypertension was achieved in 60% of patients. Normal pre-operative serum creatinine level, high pre-operative unstimulated peripheral renin levels and renal vein renin ratio of at least 1.75:1 were the most significant predictive factors for favorable outcome (p < 0.012). The pre-operative severity and duration of hypertension as well as degree of disparity in kidney sizes did not predict the post-operative improvement in renal function and blood pressure control.

Unusual Presentations of Wegener's granulomatosis: Pitfalls in Early Diagnosis.

Wegener's Granulomatosis (WG) is a disorder characterized by necrotizing granulomatous vasculitis that primarily affects the upper and lower respiratory tracts and the kidneys. Although the cause is unknown, there is strong evidence that this is an autoimmune disease and immunosuppressive therapy with cyclophosphamide and corticosteroids efficiently relieves the symptoms and, prevents relapses. We report on four cases of WG that presented with unusual features. The first patient presented with vague joint pain, blackish discoloration of the skin and leg ulcers. The second patient presented as fever of unknown origin and gingival hyperplasia. The third patient presented with hearing loss while the fourth presented with arthritis, conjunctivitis and painful swelling of the ear. It is emphasized that WG is a complex disease and can involve multiple organ systems. Early recognition and institution of proper treatment are crucial for optimal outcome.

Ischemic monomelic neuropathy: a complication of vascular access procedure.

Ischemic monomelic neuropathy (IMN) is an infrequently recognized type of ischemic neuropathy produced by shunting blood or acute occlusion of a major proximal artery in the extremities. IMN predominantly occurs in diabetic patients with evidence of peripheral atherosclerotic vascular disease and neuropathy. We report a case of ischemic monomelic neuropathy occurring in a diabetic patient with end-stage renal disease following the placement of polytetrafluoroethylene (PTFE) graft as a vascular access in the proximal upper arm for chronic hemodialysis.