M.R.N. Nampoory

Hypercoagulability, a serious problem in patients with ESRD on maintenance hemodialysis, and its correction after kidney transplantation

BACKGROUND Recurrent vascular access thrombosis (VAT) resulting in failure to continue maintenance hemodialysis (HD) therapy is not an uncommon event. The cause of VAT in these circumstances remains uncertain. We describe results of our studies to identify changes in hemostatic balance in patients on maintenance HD therapy that probably contributed to a hypercoagulable state. METHODS We studied 82 patients with end-stage renal disease on maintenance HD therapy who underwent HD for 11 to 52 months (39.3 +/- 27.4 months). Forty-nine episodes of VAT occurred in 22 patients; a single episode occurred in 12 patients; and 2 or more episodes, in 10 patients. Blood coagulation studies, including assays of inhibitors and activated protein C (PC) resistance (APCR), were performed using standard techniques. RESULTS Investigations showed the presence of lupus anticoagulant (LA) in 5.6%, anticardiolipin antibody immunoglobulin G (IgG) in 3.9% and IgM in 5.3%, APCR in 20.5%, and deficiencies in protein S (PS), PC, and antithrombin III (ATIII) in 32.1%, 24.4%, and 19.2%, respectively. When parameters were compared between patients with and without VAT episodes, LA, PC, PS, and APCR levels were significantly abnormal in those who experienced VAT. Sixteen subjects with hypercoagulable states on HD therapy underwent renal transplantation and were evaluated 9.3 +/- 4.2 months posttransplantation. Deficiencies in PC (P = 0.014), PS (P = 0.001), ATIII (P = 0.017), and APCR (P = 0.0001) were completely corrected in all subjects. CONCLUSION Hypercoagulability is a risk factor for recurrent VAT in HD patients, and renal transplantation successfully corrects these abnormalities.

Transjugular Liver Biopsy in Patients with EndStage Renal Disease

PURPOSE To assess the efficacy and safety of transjugular liver biopsy (TJLB) in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis treatment. MATERIALS AND METHODS Forty-six consecutive patients with liver disease who were undergoing hemodialysis were included in this study. An 18-gauge Tru-cut transjugular needle with a 20-mm throw was used to obtain liver tissue. All procedures were performed under fluoroscopic guidance. A single pathologist reviewed the biopsy specimens and assessed the size of fragments, number of portal tracts, and adequacy of the specimens for histologic diagnosis. All complications were recorded. The results were compared with the outcomes of percutaneous liver biopsy carried out at our institution in 32 patients with ESRD. RESULTS TJLB and percutaneous biopsy techniques yielded adequate specimens for histologic diagnosis in all patients. The mean length of the largest fragments of tissue obtained via the transjugular and percutaneous routes were 16 mm +/- 4 and 14 mm +/- 3, respectively (P = NS). There were no major complications among patients who underwent TJLB. Percutaneous liver biopsy was complicated by hemorrhage in four of 32 patients (12%), three of whom required blood transfusion. CONCLUSION TJLB is an effective and safe technique to obtain liver tissue in patients with ESRD and is associated with a lower complication rate than percutaneous liver biopsy.

Does Parathyroid Hormone Affect Erythropoietin Therapy in Dialysis Patients

Objective: The objective of this study was to assess the response to recombinant human erythropoietin (rHuEPO) during treatment of anemia in dialysis patients with hyperparathyroidism. Subjects and Methods: A total of 118 patients with stage 5 renal failure on dialysis therapy were selected for this study. Anemia was treated with rHuEPO. Laboratory data for each patient included intact parathyroid hormone (iPTH), hemoglobin (Hb), hematocrit (Hct), blood urea nitrogen, serum creatinine, calcium, phosphate, and alkaline phosphatase. Patients with iPTH >32 pmol/l were considered hyperparathyroid. Erythropoietin resistance index (ERI) was expressed as the ratio of weekly rHuEPO dose/Hct level. Results: Of the 118 patients, 83 (70.3%) were on hemodialysis (HD) and 35 (29.7%) were on continuous ambulatory peritoneal dialysis (CAPD). Sixty-three patients (64.3%) with iPTH >32 pmol/l had Hb <11 g/dl, while 34 (54.8%) with iPTH <32 had Hb >11 g/dl (p = 04). Thirty-three (56%) patients with iPTH >32 pmol/l had hemocrit <33%, while 38 (61.3%) with iPTH <32 had hemocrit <33% (p = 0.4). The median value of weekly rHuEPO dose in HD patients (12,000 units) was significantly higher in comparison with CAPD patients (6,000 units; p < 0.0001). ERI was significantly higher in HD than CAPD patients with iPTH <16 pmol/l (p = 0002) as well as with patients with 16–32 pmol/l (p = 0.012). Conclusions: CAPD patients showed a reduced requirement for rHuEPO and better control of anemia compared with HD patients. ERI was also lower in CAPD than in HD patients. Hyperparathyroidism is a parameter predictive of rHuEPO hyporesponsiveness in dialysis patients.

Xanthomonas maltophilia infection in chronic peritoneal dialysis patients

Xanthomonas maltophilia infection has only been occasionally reported in patients receiving chronic peritoneal dialysis. We describe four cases of Xanthomonas maltophilia infection associated with chronic peritoneal dialysis. Two patients presented with peritonitis and two with exit site infection. All patients were diabetics, who immediately prior to the study had not received antibiotic therapy. Failure to respond to multiple antibiotic therapy resulted in catheter removal in both patients with peritonitis. In those patients with only exit site infections, dialysis could be continued following antibiotic therapy and catheter replacement in one. Catheter loss in our patients was directly attributed to peritonitis with Xanthomonas maltophilia infection.

Blood pressure control in haemodialysis patients: An audit

Objective:  This audit was conducted to study the level of achievement of some criteria relevant to blood pressure control in haemodialysis patients and to evaluate if auditing process improves the quality of medical care given to these patients.

High incidence of post-transplant diabetes mellitus in Kuwait

Post-transplant diabetes mellitus (PTDM) has been reported to occur in 5-15% of non-diabetic renal transplant recipients. During a 15-year period (January 1983-January 1998), 631 renal transplant recipients (TxR) were followed-up in our Centre of whom 79 (12.5%) had pre-transplant diabetes mellitus. Among the 552 TxR who were non-diabetic at pre-transplantation, 117 (21.2%) developed PTDM. The gender, native renal disease and the mode of pre-transplant dialysis did not differ in those with and without PTDM. Of the 117 TxR who developed PTDM, 63 (53.8%) were above the age of 45 years where as only 90 (20.7%) of the 435 who remained non-diabetic (NDM) were above this age (P<0.05). PTDM occurred in 115 (29.6%) recipients of Arab origin (Kuwaitis and non-Kuwaitis) where as only two (1.7%) non-Arabs developed it. There was no difference in the incidence of PTDM when prednisone and azathioprine (two drug regime) were used or with cyclosporine (triple drug regime). The incidence of acute rejection episodes did not differ among PTDM and NDM groups. The over all incidence of infections requiring hospitalisation was higher in PTDM group (1.8 episodes per patient) compared to NDM group (one episode per patient) during the study period (P<0.001). Coronary heart disease was also more frequent in PTDM (15 vs. 6%, P<0.05). The cumulative graft survival at 1, 5, 10 and 14 years in the PTDM (97, 92, 74 and 67%, respectively) and NDM groups (97, 91, 80 and 73%, respectively) was similar. However, an important cause of graft loss was death of the recipient in PTDM compared to NDM (10.7 vs. 3.6%). Similarly, the patient survival up to 14 years did not differ between PTDM and NDM groups (80 and 82%, respectively), although infection related deaths were more frequent in the PTDM group (65 vs. 49%) although not statistically significant. In conclusion, there is a high incidence of PTDM in Kuwait; age and race being the two important contributory factors. The overall patient and graft survival are not adversely affected by PTDM although infections and coronary heart disease are more frequently encountered in this group.

Inferior Long-Term Outcome of Renal Transplantation in Patients with Diabetes mellitus

Objective: To retrospectively review the long-term outcome of renal transplant in diabetics at Mubarak Al-Kabeer Hospital and Hamad Al-Essa Organ Transplant Center, Kuwait from 1983 to 1998. Methods: There were 631 renal transplant patients, comprising 79 (12.5%) patients with pretransplant diabetes mellitus (pre-TDM), 117 (18.5%) patients with post-transplant diabetes mellitus and 435 (69%) nondiabetics (ND). Subjects with post-transplant diabetes mellitus were excluded from the comparative analysis. Distribution of sex, source of donors and mode of immunosuppression were similar in pre-TDM and ND groups. Results: Fifty-three (67%) recipients in pre-TDM and 90 (20.5%) in the ND group (p < 0.01) were above 45 years of age. However, 26 (33.3%) pre-TDM and 345 (79.5%) ND were below age 45. Among those who died, coronary artery disease led to death in 36% of pre-TDM and 27% in ND. Hyperlipidemia requiring drug therapy was observed in 37% pre-TDM and 6% ND. The incidence of severe infections was nearly twice in pre-TDM over ND recipients (1.9 vs. 1.0 per patient, p < 0.001). Acute rejection episodes were more frequently seen in pre-TDM (43%) than ND (33%), however the difference was not statistically significant. The patient survivals at 1, 5, 10, 14 years were significantly lower in pre-TDM (84, 65, 58 and 58%, respectively) than in ND (97, 93, 86 and 82%, respectively). The major contributory factors were severe infections and coronary artery disease. The cumulative graft survival showed a similar pattern (52% in pre-TDM, 73% in ND at 10 years). However, when death is excluded, the 10-year pure graft survival probability was similar for the pre-TDM and ND groups (76% vs. 80%). Conclusion: Our study indicates poor patient survival in pre-TDM due to coronary artery disease and infections, whereas the pure long-term graft survival was equally good in pre-TDM and ND transplant recipients.

Renal Artery Stenosis in Patients with Peripheral Vascular Disease in Kuwait

Objective: The aim of this study was to identify the incidence of atherosclerotic renal artery stenosis (RAS) in patients with peripheral vascular disease (PVD) and its relation to any known risk factors. Subjects and Methods: This prospective study was conducted on 212 patients who were subjected to peripheral angiography for symptoms of PVD over a 3-year period from 1995 to 1998 at the Mubarak Al-Kabeer Hospital, Kuwait. Angiographic evidence of atherosclerotic disease and its severity was recorded in renal, abdominal aorta, iliac, femoral, popliteal and below-knee arteries. In addition, a detailed search of identifiable risk factors was done using history, clinical examination and laboratory studies. Results: The incidence of significant atherosclerotic RAS (more than 50% diameter stenosis) in patients with PVD was 15/212 (7.07%) with no significant difference in ratio between males and females (p = 0.3) compared to that of PVD alone. Patients with common iliac and femoral artery lesions had a high incidence of RAS (93.3 and 86.7%, respectively) with more than 80% probability in RAS patients with involvement of these vessels. There was significant renal impairment (p < 0.005), as assessed by serum creatinine levels, in patients with RAS compared to those who did not have it. There was a high incidence of smoking in patients with RAS (p = 0.02), and smoking was the only risk factor identified in these subjects. Conclusions: Patients with iliac or femoral atherosclerotic disease have a high probability of associated RAS. Presence of renal impairment in patients with PVD is highly indicative of RAS. Smoking is the only identified risk factor for RAS in association with PVD in our population.

Intravenous Immunoglobulins in Lupus Nephritis

Objective: The study is aimed at demonstrating the effectiveness of intravenous immunoglobulin (IVIg) in resistant lupus nephritis. Lupus nephritis was considered resistant when it failed to show adequate clinical and laboratory response to treatment with steroid, azathioprine and pulse cyclophosphamide in combination for a period not less than 1 year. Methods: During the past 7 years 4 subjects (M = 1, F = 3) with systemic lupus erythematosus (SLE) and lupus nephritis WHO IV were selected to receive IVIg. Their age ranged from 19 to 48 years. The 3 female patients had severe extrarenal manifestations including skin rash, photosensitivity, fever, headache and severe polyarthralgia requiring large doses of analgesics. The male patient had steroid-dependent, relapsing autoimmune hemolytic anemia (AIHA) in addition to extrarenal manifestations. All subjects had microscopic hematuria, proteinuria (2–6 g/24 h), hypoalbuminemia (24–33 g/l), mild renal impairment (serum creatinine 90–160 µmol/l) and active serology for SLE. These patients had not responded satisfactorily to several courses of steroids, azathioprine and pulses of intravenous cyclophosphamide in 23–180 months. All 4 patients were started and continued on IVIg as per our protocol. Results: During the 9 months to 7.5 years of follow-up, these patients showed excellent response to IVIg. Their extrarenal symptoms had totally disappeared, serological activity subsided, proteinuria decreased (0.5–2 g/24 h), serum albumin improved (30–42 g/l) and renal function remained stable. The subject with AIHA did not suffer any further relapses and his hemoglobin remained above 110 g/l with only 10 mg of prednisolone daily. Repeat renal biopsy done in 2 patients showed definite histological reversal of active lesions. Clinical and immunological improvements might be related to the modulation of macrophage T cell function and enhancement of suppressor T cell function. Conclusion: IVIg has shown excellent therapeutic effect as an alternative drug in treatment of renal and extrarenal manifestations of SLE, which are resistant to other modalities of treatment.

Cyclosporine microemulsion formulation (sigmasporin microral) effect as first-line immunosuppressant on renal functions at 3 years.

BACKGROUND Cyclosporine (CsA) remains a mainstay of immunosuppressive maintenance regimens in developing countries, but its effects on long-term kidney allograft survival are still unclear. Our aim was to assess a generic microemulsion CsA (Sigmasporin) for long-term impact on graft function and patient survival among stable renal transplant patients. METHODS Over a 36-month period, patients with transplantations from >6 months earlier were maintained on CsA doses of 2-8 mg/kg/d to keep C(2) within the recommended therapeutic range. We assessed 25 efficacy and tolerability parameters of scheduled intervals. RESULTS Twenty-seven patients (9 female, 18 male) from 6 centers in 4 Middle-Eastern countries were enrolled between 2004 and 2009. Their average age was 35.1 ± 9.8 years, body mass index ranged from 15.7 to 41.2 kg/m(2), and average time from transplantation was 2.2 ± 1.6 years. Within the 36-month observation period the CsA dose was reduced by 17.3% from 2.89 ± 0.88 mg/kg/d to achieve C(2) levels of 600-1000 ng/mL. After 36 months the glomerular filtration rate declined by 8.2% from an overall baseline mean of 72.7 ± 23.5 mL/min/1.73 m(2). It improved in 11.1% of patients and remained unchanged in 44.4%. No new cases of hypertension or diabetes mellitus were reported, and there was 1 case of borderline hyperlipidemia. Graft functions were stable, apart from 2 incidences of CsA nephrotoxicity. Both graft and patient 3-year survival rates were 100%. CONCLUSIONS On a 3-year basis, Sigmasporin Microral was effective to maintain stable renal functions in kidney transplant patients, with safety and tolerability profiles similar to those reported in the international literature.