Renal replacement therapy in Nepal

Renal replacement therapy in Nepal fulfills only a small part of the current needs, with 97 hemodialysis machines available for the general population of 29 million. Transportation difficulties to dialysis centers preclude many of the patients from end-stage renal disease care, due to the rural nature of the population. Peritoneal dialysis (PD) organized into rural sub segments, considering the Mexican model of PD and government funding appear to offer some solution to provision of care for this mountainous rural country. We review the current statistics of dialysis patients, hemodialysis numbers, and renal transplantations within Nepal and offer suggestions regarding possibilities for increasing renal care within the country.     

Acute renal failure and chronic kidney disease following liver transplantation

Acute renal failure (ARF) and chronic kidney disease (CKD) are common complications after liver transplantation (LTx). The incidence of ARF post-LTx varies between 48% and 94%; 8% to 17% of patients require renal replacement therapy (RRT). The most common cause of ARF early after LTx is ischemic acute tubular necrosis, followed later by cyclosporine toxicity and sepsis. Preoperative serum creatinine >1.5 mg/dL and early hepatic allograft dysfunction are risk factors for the occurrence of postoperative ARF. Of patients with ARF due to the hepatorenal syndrome, approximately two-thirds will recover, although recovery may be delayed 3 months or longer after LTx. Mortality after LTx is affected modestly by the presence of ARF pretransplant (<2-fold increase), but increases markedly (up to 8-fold) in the face of ARF posttransplant. Mortality does not appear to be influenced by the mode of RRT used. The risk of CKD after LTx is approximately 18% at 5 years and increases to approximately 25% by 10 years after transplantation. Calcineurin inhibitor toxicity is the most common cause. Specific prognosticators for predicting CKD after LTx are presently lacking. The occurrence of CKD after LTx markedly impairs long-term survival.     

Free dialysis in Nepal: Logistical challenges explored

Nepal's Ministry of Health began offering free lifetime hemodialysis (HD) in 2016. There has been a large growth in renal replacement therapy (RRT) services offered in Nepal since 2010, when the last known data on the subject was published. In 2016, 42 HD centers existed (223% increase since 2010) serving 1975 end stage renal disease patients (303% increase since 2010); 36 nephrologists were registered (200% increase since 2010), 12 were trained in transplantation, and 790 transplants had been performed to date. We estimate the incidence of end stage renal disease to be 2900 patients (100 per million population). With an annual cost of approximately US$2300 per dialysis patient, offering free dialysis could potentially cost the government US$6.7 million per year, suggesting that 2.1% of the annual health budget would be allocated to 0.01% of the population. The geographic zone surrounding the capital city, Kathmandu, contains 50% of HD centers, but only 14.5% of Nepal's population. Forty‐eight percent of the population lives within zones without HD service, therefore infrastructure challenges exist in providing equitable access to RRT. The aim of this article is to summarize the current statistics of RRT in Nepal.     

Effect of supportive extracorporeal treatment in liver transplantation recipients and advanced liver failure patients

Recently, continuous venovenous hemodiafiltration (CVVHDF) and plasmapheresis (PF) were suggested as supportive therapy options in combination with standard treatment in advanced liver failure. The aim of this study was to analyze the effects of supportive extracorporeal treatment (SET) in a group of patients with advanced hepatic failure. A total of 25 patients (7 women, 18 men; mean age, 39.3+/-15.4 years; 13 were transplant recipients [6 women, 7 men; mean age, 37.7+/-16.9 years]) were included. All patients were in hepatic coma and receiving standard coma and liver failure management when they received SET. Number of SET sessions; levels of serum blood urea nitrogen, creatinine, albumin, calcium, phosphorus, ammonia, alanine and aspartate aminotransferase, and total/conjugated bilirubin; and prothrombin times (PTT) before and after SET were recorded retrospectively. 7.7+/-7.9 SET sessions were performed. Thirteen liver transplant recipients required SET for an average of 9.7+/-8.3 days after transplantation. Serum ammonia and bilirubin levels were lower after termination of supportive therapy when compared with initial levels (p<0.0001 and p<0.005 respectively). During follow-up, hepatic encephalopathy and liver failure resolved in 11 patients, while 14 patients (7 transplant recipients) died. There was no significant difference between patients in either group except that PTT was shorter in patients who survived (p<0.01). Further analyses revealed that in surviving patients, ammonia clearance was higher (p<0.01). In patients with advanced liver failure, or liver transplants, CVVHDF and/or PF could be supportive options combined with standard treatment.     

Complete remission of renal cell carcinoma with lung metastases in two hemodialysis patients after low-dose interferon therapy

A standard immunotherapy strategy for metastatic renal cell carcinoma (RCC) in dialysis patients has yet to be established. In this study, we report complete remission of RCC with lung metastases in 2 hemodialysis patients after low‐dose interferon therapy (Sumiferon^® 3 × 10⁶ international unit 3 times a week). These results suggest that interferon therapy is important for clear cell RCC with lung metastases in dialysis patients, even in the era of molecular‐targeted therapies.     

Online hemodiafiltration: 4 years of clinical experience

Online hemodiafiltration (online HDF) is a new hemodialysis technique combining convection and diffusion and thus also enabling the purification of large molecules. As yet, only a small number of clinical experiences have been published about the effectiveness and safety of online HDF. We present a prospective and observational study conducted on 31 patients treated with online HDF in our center in the last 4 years. The purpose of the study is to compare the evolution of the following aspects before and after starting online HDF: dose of dialysis, purification of medium-sized/large molecules, inflammation, nutrition, Ca-P metabolism, anemia, and intradialytic complications. Online HDF increased Kt/V to 31.0% (p > 0.001) and reduced postdialysis beta(2)-M to 66.4% (p > 0.001). The rest of the parameters analyzed did not vary significantly. During online HDF, episodes of symptomatic hypotension fell by 45% in relation to conventional hemodialysis, and no relevant complication occurred. Online HDF is very useful in patients in whom we need to increase replacement therapy, such as patients with a large body surface, those in whom we suspect a residual syndrome or those who have been receiving dialysis for a long time and for whom we wish to prevent amyloidosis. Online HDF is safe and better tolerated than conventional hemodialysis.     

Anticoagulation,delivered dose and outcomes in CRRT: The program to improve care in acute renal disease (PICARD)

Delivered dialysis dose by continuous renal replacement therapies (CRRT) depends on circuit efficacy, which is influenced in part by the anticoagulation strategy. We evaluated the association of anticoagulation strategy used on solute clearance efficacy, circuit longevity, bleeding complications, and mortality. We analyzed data from 1740 sessions 24 h in length among 244 critically ill patients, with at least 48 h on CRRT. Regional citrate, heparin, or saline flushes was variably used to prevent or attenuate filter clotting. We calculated delivered dose using the standardized Kt/V_urea. We monitored filter efficacy by calculating effluent urea nitrogen/blood urea nitrogen ratios. Filter longevity was significantly higher with citrate (median 48, interquartile range [IQR] 20.3–75.0 hours) than with heparin (5.9, IQR 8.5–27.0 hours) or no anticoagulation (17.5, IQR 9.5–32 hours, P < 0.0001). Delivered dose was highest in treatments where citrate was employed. Bleeding complications were similar across the three groups (P = 0.25). Compared with no anticoagulation, odds of death was higher with the heparin use (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.02–3.32; P = 0.033), but not with citrate (OR 1.02 95% CI 0.54–1.96; P = 0.53). Relative to heparin or no anticoagulation, the use of regional citrate for anticoagulation in CRRT was associated with significantly prolonged filter life and increased filter efficacy with respect to delivered dialysis dose. Rates of bleeding complications, transfusions, and mortality were similar across the three groups. While these and other data suggest that citrate anticoagulation may offer superior technical performance than heparin or no anticoagulation, adequately powered clinical trials comparing alternative anticoagulation strategies should be performed to evaluate overall safety and efficacy.     

Continuous Renal Replacement Therapy for Liver Disease

Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for critically ill patients with acute renal failure around the world. In particular, CRRT is used for patients with combined liver and acute renal failure, because they are often hemodynamically unstable. The question arises as to whether the use of CRRT should be extended to those patients with acute and chronic liver failure who do not have dialysis-dependent renal failure. CRRT could potentially allow some detoxification by removing water-soluble toxins and also allow regulation of intravascular volume and correction of sodium and other electrolyte and acid–base imbalances. By providing homeostatic control, CCRT could potentially help support patients by bridging to liver transplantation and managing those who eventually recover with hepatic regeneration.     

Survival to discharge among patients treated with continuous renal replacement therapy

Continuous renal replacement therapy (CRRT) is widely used in critically ill patients with acute renal failure (ARF). The survival of patients who require CRRT and the factors predicting their outcomes are not well defined. We sought to identify clinical features to predict survival in patients treated with CRRT. We reviewed the charts of all patients who received CRRT at the Toronto General Hospital during the year 2002. Our cohort (n=85) represented 97% of patients treated with this modality in 3 critical care units. We identified demographic variables, underlying diagnoses, transplantation status, location (medical-surgical, coronary, or cardiovascular surgery intensive care units), CRRT duration, baseline estimated glomerular filtration rate (eGFR), and presence of oliguria (<400 mL/day) on the day of CRRT initiation. The principal outcome was survival to hospital discharge. Among those alive at discharge, we assessed whether there was an ongoing need for renal replacement therapy. Greater than one-third (38%, 32/85) of patients survived to hospital discharge. Three (9%) survivors remained dialysis-dependent at the time of discharge. Survivors were younger than nonsurvivors (mean age 56 vs. 60 years), were on CRRT for a shorter duration (7 vs. 13 days), and had a higher baseline eGFR (74 vs. 62 mL/min/m(2)). Patient survival varied among different critical care units (medical surgical 33%, coronary 38%, and cardiovascular surgery 45%). Multivariable logistic regression revealed that shorter duration of CRRT, nonoliguria, and baseline eGFR >60 mL/min/m(2) were independently associated with survival to hospital discharge (p<0.05). Critically ill patients with ARF who require CRRT continue to have high in-hospital mortality. A shorter period of CRRT dependence, nonoliguria and higher baseline renal function may predict a more favorable prognosis. The majority of CRRT patients who survive their critical illness are independent of dialysis at the time of hospital discharge.     

A case of gabapentin‐induced rhabdomyolysis requiring renal replacement therapy

Gabapentin is commonly used for controlling convulsions, restless pain syndrome, and pain in diabetic neuropathy. Common side effects include dizziness, somnolence, ataxia, peripheral edema, and confusion; gabapentin‐induced rhabdomyolysis is rarely reported. To date, the reported cases of gabapentin‐induced rhabdomyolysis have been associated with patients with multiple underlying diseases and assuming multiple medicines for various reasons. In this report, we describe a case of gabapentin‐induced rhabdomyolysis in a 32‐year‐old woman with no medical history. We also review related literature and discuss the possible mechanism and the association with other factors. This case shows that gabapentin can induce rhabdomyolysis in healthy patients and that clinicians must consider the possible association between gabapentin and rhabdomyolysis.     

Continuously functioning artificial nephron system: the promise of nanotechnology

Nearly 900,000 patients worldwide have end-stage renal disease and require dialysis or kidney transplantation. Despite the availability of these forms of renal replacement therapy for nearly four decades, mortality and morbidity are high and patients often have a poor quality of life. We have developed a human nephron filter (HNF) utilizing nanotechnology that would eventually make feasible a continuously functioning, wearable or implantable artificial kidney. The device consists of two membranes operating in series within one device cartridge. The first membrane mimics the function of the glomerulus, using convective transport to generate a plasma ultrafiltrate containing all solutes approaching the molecular weight of albumin. The second membrane mimics the function of the renal tubules, selectively reclaiming designated solutes to maintain body homeostasis. No dialysis solution is used in this device. The HNF has been computer-modeled, and operating 12 hr per day, 7 days per week the HNF provides the equivalent of 30 mL/min glomerular filtration rate (compared to half that amount for conventional thrice-weekly hemodialysis). Animal studies should begin in the next 1 to 2 years, and clinical trials would then follow 1 to 2 years subsequent. The HNF system, by eliminating dialysate and utilizing a novel membrane system created through applied nanotechnology, represents a breakthrough in renal replacement therapy based on the functioning of native kidneys. The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life.     

Importance of early dialysis for acute renal failure after an open-heart surgery

Coronary artery disease is a major cause of death in patients with a renal dysfunction. Among the patients who undergo coronary artery bypass grafting, renal dysfunction is known to be a major predictor of in-hospital and out-of-hospital mortality. From 2004 to 2007, we performed elective open-heart surgeries on 2380 patients in whom there was no primary renal failure. Of those patients, only 185 in whom acute renal failure (ARF) was developed were included in the study. The patients were divided into 2 groups: a late dialysis group (n=90) and an early dialysis group (n=95). The mean age of the patients was 62.3±6.4 in the late dialysis group and 64.5±5.2 in the early dialysis group. There were 32 female and 58 male patients in the late dialysis group and 36 female and 59 male patients in the early dialysis group. Acute renal failure developed only in 185 patients out of 2380 open-heart surgery patients. The overall mortality in the 2380 open-heart surgery patients was 1.97%. Mortality among the ARF patients was 5.9%. However, there was no significant difference in hospital mortality between the 2 groups. Major complications, such as postoperative pneumonia, prolonged ventilation time, arrhythmia, the number of times postoperative hemodialysis was performed, development of chronic renal failure, time spent in the intensive care unit and the period of hospitalization, sepsis, and low cardiac output, were significantly higher in the late dialysis group. There was no difference in mortality between the 2 groups. Early dialysis for open-heart surgery patients who develop ARF postoperatively does not decrease mortality. However, it decreases morbidity, the amount of time spent in intensive care, and the period of hospitalization and thus reduces patient costs.     

Fluid overload and acute kidney injury

Acute kidney injury is commonly encountered in critically ill patients, and is associated with worse outcomes. Fluid therapy is a key component in the management of these patients, often leading to fluid overload, especially in the setting of septic acute kidney injury. Emerging data overwhelmingly suggest that fluid overload in these patients may be associated with adverse outcomes. Management of such patients should include a strategy of early guided resuscitation, followed by careful assessment of fluid status, and early initiation of renal replacement therapy as soon as it is deemed safe, aiming for a neutral or negative fluid balance. This review will focus on the pathophysiological link between fluid overload and acute kidney injury, mechanisms of organ dysfunction in fluid overload, and strategies for management.