Darbepoetin Use for the Treatment of Anemia in Hemodialysis Patients in Saudi Arabia

Erythropoietin replacing proteins have improved patient outcomes and quality of life. Darbepoetin has a 3-fold longer half-life than recombinant human erythropoietin (rHuEPO). In this study, we investigate the efficacy and safety of the conversion of stable hemodialysis patients from the current short-acting r-HuEPO (EPO alfa or beta) to the long-acting darbepoetin. In addition, we verified the appropriateness of the current ratio of conversion of the short acting to the long-acting erythropoietin in an open label prospective multi-center study. The study design included 12 weeks darbepoetin administration. The conversion ratio was 200 IU of short acting r-HuEPO to 1 microgram of darbepoetin. We adjusted the dose of darbepoetin to maintain hemoglobin levels between 110-120 g/L. There were 33 patients who satisfied the entry criteria. The study was conducted from January-June, 2005. The study patients included 18 men and 15 women, the mean age was 50.4 ± 12.3 years and the mean duration on HD was 323 ± 51.9 days. There was a significant decrease in the mean dose of darbepoetin from 37.3 ± 12.9 ug/week at week 1 of the study to 20.8 ± 16.6 ug/week by the end of week 12 (p< 0.00003) while the hemoglobin level was maintained within the previously defined range. The initial conversion ratio from short-acting erythropoietin to darbepoetin was 200 IU to 1 microgram. However, at the end of week 12, the mean dose of darbepoetin decreased to an equivalent conversion ratio to 361 IU: 1 microgram. This may reflect great savings in the cost of treatment. Our experience with darbepoetin reveals that darbepoetin is effective and safe for the treatment of anemia in hemodialysis patients and has a more convenient dosing schedule than short-acting erythropoietin. The darbepoetin dosage decreases over time and savings are expected to greater with darbepoetin more than with short-acting erythropoietin with time

Serum cystatin C: A surrogate marker for the characteristics of peritoneal membrane in dialysis patients

To evaluate whether cystatin C levels can be a surrogate marker of creatinine clearance and reflect the characteristics of peritoneal membrane in dialysis patients, we performed peritoneal equilibration tests (PET) in 18 anuric adult chronic peritoneal dialysis (PD) patients with a mean age of 39.7 ± 20 years. All the samples were analyzed for urea, creatinine, and cystatin C. Peritoneal transport, mass transfer, and peritoneal clearance of cystatin C were calculated. Correlation and regression analysis was done using cystatin C as a dependent variable and age, sex, height, weight, body surface area, and creatinine as independent variables. Cystatin C demonstrated a significant time dependent increase of dialysate concentration and decline in the serum concentrations during PET, and a strong correlation between serum creatinine and serum cystatin C concentrations(r: 0.62, p= 0.008). The trans-peritoneal clearance (mL/min/1.73 m 2 ) of cystatin C was related to its serum concentration and was similar to creatinine in its pattern but of smaller magnitude. Peritoneal mass transfer (mg/4 hr per 1.73 m 2 ) for cystatin C serum creatinine was 1.68 ± 0.67 and 73.3 ± 29.8, respectively. The dialysis/plasma D/P cystatin C concentration was > 0.1 at 4 hrs of PET denoted high peritoneal transport, while the values of < 0.1 denoted low transport type. We conclude that cystatin C follows the same pattern of peritoneal exchange as creatinine but the magnitude of transfer is many folds lower than creatinine. At present clinical utility of cystatin C in the evaluation of solute clearance is probably limited due to the minute amounts transferred across the membrane and the high renal clearance in the presence of residual renal function

Prevalence of Hepatitis B core antibodies with negative Hepatitis B surface antigen in dialysis and chronic kidney disease patients

Occult hepatitis B infection (OBI) is a potential cause of infection transmission in patients with chronic kidney disease (CKD) and dialysis-dependant patients. It is liable to be missed since the marker for OBI, hepatitis B core antibody (HBcAb), is not done routinely. We carried out a study to assess the prevalence of OBI in CKD Stage II–V or requiring renal replacement therapy. It was a cross-sectional study carried out at Fatima Memorial Hospital, Lahore, from May 2104 to May 2015. A total of 188 patients were included in this study, 124 were dialysis dependent and 64 had acute or CKD Stage II–V. About 17.55% (n = 33) of patients had isolated HBcAb positive. Nearly 33.5% (n = 63) of patients were found to have hepatitis B surface antigen positive, indicating development of immunity by exposure to virus. About 20.74% (n = 39) of patients were co-positive with HBcAb also. The prevalence of isolated HBcAb in dialysis and CKD patients is high; therefore, testing for HBcAb should be a routine part of screening in our CKD population to rule out OBI. Further confirmation with polymerase chain reaction analysis for HBV viral DNA is recommended. Considering our circumstances, a consensus statement from the hepatologists and nephrologists is needed to further plan for the management of such cases

Hepatitis G virus (HGV) infection in Saudi dialysis patients and healthy controls

Background: Viral hepatitis is a global health problem with a high mortality rate. End stage renal disease (ESRD) patients have a high prevalence of Hepatitis B and C virus infection. Present study was done to identify the prevalence and course of a new isolate Hepatitis G virus (HGV) infection in Saudi dialysis patients. Methods: The pattern of viral hepatitis infection (HBV. HCV and HGV) was investigated in 109 Saudi patients with ESRD and 100 healthy Saudi blood donors. Donated blood was tested for markers of Hepatitis B, C and G viruses. Liver functions were measured and blood picture and liver biopsies were also performed at regular intervals. Results: Out of the 109 ESRD patients 68 (62.4%) were positive for at least one viral marker: 59 (54.1%) were positive for HCV, six (5.5%) were positive for HGV and three (2.8%) were positive for HBsAg. Four of the six HGV positive patients were also co-infected with HCV. Eight (8%) of the blood donors were positive for at least one viral marker. Elevated ALT levels (>4 times normal) were recorded in four out of the six HGV-positive patients including three co-infected with HCV. Conclusions: Our results are in agreement with similar studies from different countries and also raise the question about the causal relationship between HGV and liver disease among dialysis patients

Normal Reference Levels of Serum Cystatin C in Saudi Adults

This is the first report from Saudi Arabia studying the normal reference intervals in adult Saudi subjects and evaluating serum cystatin C as a prospective marker for the assessment of the glomerular filtration rate (GFR). Three hundred healthy adult Saudi subjects including 156 males (52%) and 144 females (48%), with a mean age of 31.21 ± 9.82 years were prospectively studied to establish normal reference ranges for cystatin C. A total of 68.34% of the study patients were in the age-group of 21-40 years. The mean serum cystatin C in the 300 healthy subjects was 0.751 ± 0.11 mg/L (0.50 - 1.09), increasing gradually with age: it was 0.738 ± 0.11 mg/L (0.51 - 1.09) in the age-group 21 - 30 years and 0.807 ± 0.12 (0.51 - 1.09) among subjects who were > 50 years of age. The mean serum cystatin C in females (0.778 ± 0.118 mg/L) was significantly hig-her than in males (0.726 ± 0.095 mg/L) (p < 0.0001). The serum cystatin C level was within the defined reference range of 0.53 - 0.95 mg/L in 95% of the subjects with a mean value of 0.74 ± 0.097 mg/L, and was falling within the 95% confidence interval of 0.73865 - 0.7637 mg/L, and with 98.84% area under the curve (AUC). All the other renal function markers (urea, serum crea-tinine, calculated GFR, BMI) among the studied subjects were within the normal reference ranges for adult Saudi population. The serum cystatin C level had a significant correlation with the body mass index (BMI) (r = 0.155; p = 0.007) and a correlation with serum creatinine as well (r = 0.009; p = 0.873). It showed a negative correlation with calculated GFR as per Cockroft-Gault equation (r = - 0.101; p = 0.083)

Cardiac output and urea kinetics in dialysis patients: Evidence supporting the regional blood flow model

Cardiac output and urea kinetics in dialysis patients: Evidence supporting the regional blood flow model. The regional blood flow model predicts that urea sequestration occurs in organs rather than cells, and that post-dialysis urea rebound is a function of both cardiac index (CI) and regional blood flow distribution to muscle. We measured cardiac output (CO) in 100 randomly selected dialysis patients using bioelectric impedance three times during a single dialysis. Mean CO was 5.8 ± 2.1 liter/min and CI averaged 3.1 ± 1.1 liter/min/M2, CI was negatively correlated with age (r = -0.48, P < 0.01). CI was strongly affected by vasodilator ingestion (yes, N = 36, CI = 3.5 ± 1.2; no, N = 64, CI = 2.88 ± 0.92, P < 0.006). CI was not associated with systolic, diastolic, or mean blood pressures, nor with Hct, although very few severely anemic patients were in the cohort. Repeat intra-dialytic CO measurements two to three months later in 15 patients with low CI (2.59 ± 0.59 liter/min/M2) and in 13 patients with high CI (5.00 ± 0.9, P < 0.001) during a urea kinetic modeling session including 30 minutes post-dialysis rebound, sampling showed highly reproducible values for CO, with a mean absolute value % difference between CO values measured several months apart of 9.0 ± 17%, r = 0.92. Urea rebound expressed as the difference (ΔKt/V30) between equilibrated and single-pool Kt/V was lower in the high CI group (-0.099 ± 0.07) than in the low CI group (-0.16 ± 0.06, P = 0.026), and ΔKT/V30 as well as ΔKt/V30 divided by K/V correlated with CI (r = 0.48 and 0.48, respectively, P < 0.01). The RBF model was used to compute a group mean predicted ΔKt/V30 for the low CI and high CI groups based on measured group mean values for CI and K/V. The predicted ΔKt/V30 values for the high CI group (-0.097) and the low CI group (-0.183) agreed closely with measured values. RBF modeled values of CO (7.46 ± 2.96 liter/min) were not significantly different from impedance-derived CO (6.93 ± 2.70 liter/min), and the two CO measures correlated significantly (r = 0.63, P = 0.0003). The results provide support for the regional blood flow model of urea kinetics

Living Unrelated Renal Transplant: Outcome and Issues

Living unrelated transplantation (LURT) is emerging as a practical option in renal transplantation due to shortage of living related and cadaver donors. We report a six-years (December 1991 to December 1996) follow-up of 60 LURT patients. The majority of these patients (95&#x0025;) were transplanted outside the Kingdom of Saudi Arabia; 37 in India, 14 in Egypt, five in the USA and one in Pakistan. Only three patients (emotionally related) were transplanted in Saudi Arabia. Before transplantation, 50 (83.4&#x0025;) patients were on chronic hemodialysis, three (5&#x0025;) on peritoneal dialysis and three (5&#x0025;) were transplanted pre-emptively. Post-operatively, the majority of the study patients were on three drug immunosuppressive therapy. One and five year graft survival was 93.0&#x0025; and 59.6&#x0025;, while patient survival at one and three years was 93.7&#x0025; and 81&#x0025;, respectively. Surgical complications included lymphocele in 10&#x0025; of the study patients, urinary leak in 8.3&#x0025;, and bleeding from the vascular anastomosis in 6.6&#x0025;. There were eight episodes of acute rejection in eight (13.3&#x0025;) patients and all episodes were successfully treated; two patients required monoclonal anti-lymphocyte antibodies (OKT3). Eleven (18.3&#x0025;) patients developed chronic rejection, which resulted in the loss of ten (90&#x0025;) allografts. Infection was the commonest cause for hospital admission; urinary tract infection (UTI) being responsible for 40&#x0025; of admissions. Three patients had Cytomegalovirus pneumonia, one had Pneumocystis Carinii pneumonia and one had candida pneumonia. Two (3&#x0025;) patients developed Kaposi&#x2032;s sarcoma. We conclude that LURT can help in overcoming the shortage of organs for transplant, however, commercial transplantion in developing countries is associated with high morbidity and mortality

Validation of predictive equations for glomerular filtration rate in the Saudi population

Predictive equations provide a rapid method of assessing glomerular filtration rate (GFR). To compare the various predictive equations for the measurement of this parameter in the Saudi population, we measured GFR by the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formulas, cystatin C, reciprocal of cystatin C, creatinine clearance, reciprocal of creatinine, and inulin clearance in 32 Saudi subjects with different stages of renal disease. We com-pared GFR measured by inulin clearance and the estimated GFR by the equations. The study included 19 males (59.4&#x0025;) and 13 (40.6&#x0025;) females with a mean age of 42.3 &#177; 15.2 years and weight of 68.6 &#177; 17.7 kg. The mean serum creatinine was 199 &#177; 161 &#956;mol/L. The GFR measured by inulin clearance was 50.9 &#177; 33.5 mL/min, and the estimated by Cockcroft-Gault and by MDRD equations was 56.3 &#177; 33.3 and 52.8 &#177; 32.0 mL/min, respectively. The GFR estimated by MDRD revealed the strongest correlation with the measured inulin clearance (r= 0.976, P= 0.0000) followed by the GFR estimated by Cockcroft-Gault, serum cystatin C, and serum creatinine (r= 0.953, P= 0.0000) (r= 0.787, P= 0.0001) (r= -0.678, P= 0.001), respectively. The reciprocal of cystatin C and serum creatinine revealed a correlation coefficient of 0.826 and 0.93, respectively. Cockroft-Gault for-mula overestimated the GFR by 5.40 &#177; 10.3 mL/min in comparison to the MDRD formula, which exhibited the best correlation with inulin clearance in different genders, age groups, body mass index, renal transplant recipients, chronic kidney disease stages when compared to other GFR predictive equations