Glycemic Control and Burnt‐Out Diabetes in ESRD

Treatment of early diabetes mellitus, the most common cause of chronic kidney disease (CKD), may prevent or slow the progression of diabetic nephropathy and lower mortality and the incidence of cardiovascular disease in the general diabetic population and in patients with early stages of CKD. It is unclear whether glycemic control in patients with advanced CKD, including those with end‐stage renal disease (ESRD) who undergo maintenance dialysis treatment is beneficial. Aside from the uncertain benefits of treatment in ESRD, hypoglycemic interventions in this population are also complicated by the complex changes in glucose homeostasis related to decreased kidney function and to dialytic therapies, occasionally leading to spontaneous resolution of hyperglycemia and normalization of hemoglobin A1c levels, a condition which might be termed “burnt‐out diabetes.” Further difficulties in ESRD are posed by the complicated pharmacokinetics of antidiabetic medications and the serious flaws in our available diagnostic tools used for monitoring long‐term glycemic control. We review the physiology and pathophysiology of glucose homeostasis in advanced CKD and ESRD, the available antidiabetic medications and their specifics related to kidney function, and the diagnostic tools used to monitor the severity of hyperglycemia and the therapeutic effects of available treatments, along with their deficiencies in ESRD. We also review the concept of burnt‐out diabetes and summarize the findings of studies that examined outcomes related to glycemic control in diabetic ESRD patients, and emphasize areas in need of further research.     

Antihypertensive Medications in End‐Stage Renal Disease

Hypertension is almost universal in end‐stage renal disease (ESRD) and contributes to the substantial cardiovascular (CV) morbidity and mortality observed in these patients. The management of blood pressure (BP) in ESRD is complicated by a number of factors, including missed dialysis treatments, intradialytic changes in BP, medication removal with dialysis, and poor correlation of BPs obtained in the dialysis unit with those at home and with CV outcomes. Control of extracellular volume with ultrafiltration and dietary sodium restriction represents the principal strategy to manage hypertension in ESRD, and antihypertensive medications are subsequently added if this strategy is inadequate. While reduction in BP with medication improves CV outcomes, few head‐to‐head clinical trials have been performed to firmly establish the superiority of one antihypertensive medication class over another. Therefore, individualization of therapy is necessary, and patient comorbidities must be considered. Angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta‐blockers are reasonable first‐line agents for most patients. ACE inhibitors and ARBs exert cardioprotective effects that are independent of BP reduction. Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension. Intradialytic hypertension can be managed with challenging the patient's dry weight and using nondialyzable medications. Within a class of antihypertensive medications, there may be large variability in drug removal with dialysis, which must be considered upon medication selection. Studies demonstrate that even thrice‐weekly dosing of medication after dialysis has robust BP‐lowering effects, which may be a useful regimen in nonadherent patients.     

Updates on the Management of Diabetes in Dialysis Patients

Diabetes mellitus is the leading cause of end‐stage renal disease (ESRD) in the U.S. and many countries globally. The role of improved glycemic control in ameliorating the exceedingly high mortality risk of diabetic dialysis patients is unclear. The treatment of diabetes in ESRD patients is challenging, given changes in glucose homeostasis, the unclear accuracy of glycemic control metrics, and the altered pharmacokinetics of glucose‐lowering drugs by kidney dysfunction, the uremic milieu, and dialysis therapy. Up to one‐third of diabetic dialysis patients may experience spontaneous resolution of hyperglycemia with hemoglobin A1c (HbA1c) levels <6%, a phenomenon known as “Burnt‐Out Diabetes,” which remains with unclear biologic plausibility and undetermined clinical implications. Conventional methods of glycemic control assessment are confounded by the laboratory abnormalities and comorbidities associated with ESRD. Similar to more recent approaches in the general population, there is concern that glucose normalization may be harmful in ESRD patients. There is uncertainty surrounding the optimal glycemic target in this population, although recent epidemiologic data suggest that HbA1c ranges of 6% to 8%, as well as 7% to 9%, are associated with increased survival rates among diabetic dialysis patients. Lastly, many glucose‐lowering drugs and their active metabolites are renally metabolized and excreted, and hence, require dose adjustment or avoidance in dialysis patients.     

Health economics of renal replacement therapy: perspectives from Singapore

The prevalence of end-stage renal disease (ESRD) in Singapore is high and projected to increase sharply due to the aging population and the high prevalence of diabetes. The number of patients treated with dialysis was projected to rise from 2633 in 1999 to nearly 6000 in the year 2010. The cost of dialysis provision was estimated to increase 2.5-fold from US dollar 90 million in 1999 to US dollar 241 million in 2010. To address this, the Singapore Ministry of Health launched three initiatives in the year 2000: First, to reduce the incidence of ESRD through (1) primary prevention of diabetes, (2) community-based screening to facilitate early detection of patients with diabetes, (3) improving glycemic and blood pressure (BP) control of diabetics in the primary care setting, and (4) the establishment of dedicated Renal Retardation clinics to optimize BP control (and glycemic control for diabetics), and reduce the level of proteinuria in patients at high risk of ESRD development. Second, to increase the percentage of ESRD patients treated with continuous ambulatory peritoneal dialysis (CAPD), which is a lower-cost modality compared with hemodialysis; and third, amendments to the existing opt-out legislation for organ procurement for transplantation to increase the supply of kidneys for cadaveric renal transplant.     

Outcomes research in dialysis

Worldwide, the number of patients with end stage renal disease (ESRD) and the number of ESRD patients receiving renal replacement therapy is growing. In the United States the number of patients enrolled in the Medicare-funded ESRD program has grown substantially, from approximately 10000 beneficiaries in 1973 to 340261 as of December 31, 1999. United States has the highest incidence ESRD of 317 per million population. Despite the magnitude of resources committed to the treatment of ESRD and the substantial improvements in the quality of dialysis therapy, these patients continue to experience significant mortality and morbidity, and reduced quality of life. Moreover, 50% of dialysis patients have 3 or more comorbid conditions, the mean number of hospital days per year is approximately 14 per patient, and self reported quality of life is far lower in dialysis patients than in general population. The most desirable interventions are those that specifically target measurable global outcomes such as mortality, morbidity, and health care costs. Nevertheless, patient outcomes that have shown links with these global outcomes may also be appropriate targets for intervention. This article will briefly review the available literature to discuss the role of important clinical indicators on dialysis outcomes and their impact on continuing care of ESRD population.     

Funding ESRD care through charity: the paradigm of the National Kidney Foundation of Singapore.

Given the prohibitive costs of end-stage renal disease (ESRD) care for certain countries and the increasing incidence of ESRD worldwide, alternative methods of funding dialysis care are increasingly necessary. We describe the paradigm of the National Kidney Foundation of Singapore (NKF-S), the provider of subsidized dialysis care and comprehensive rehabilitative services to approximately 60% of all ESRD patients in the country, whose activities are funded entirely by charitable public donations. Unique to the NKF-S model are the considerations of the donor as an "investor" in the health care of NKF-S dialysis patients, the personal responsibility of the dialysis patient as a recipient of this "investment" to play an active role in achieving good clinical and rehabilitative outcomes, and the fostering of community-based support systems to facilitate patient rehabilitation such as partnerships with employers willing to employ dialysis patients. The success of the system is shown by its clinical outcomes, which approximate those observed in the United States. We believe that several aspects of the NKF-S model for ESRD care may be implemented in other communities, particularly in countries that have yet to develop financially and clinically mature dialysis programs.     

Intensive Hemodialysis in the (Nursing) Home: the Bright Side of Geriatric ESRD Care?

Elderly ESRD patients often lose functionality when they start dialysis, which may be due to a variety of clinical problems. We recently postulated that intensive (longer and/or more frequent) hemodialysis (HD) may be the ideal strategy to try to prevent these ESRD‐ and dialysis‐related complications, including dialysis‐induced hypotension, cardiac and cerebral events, malnutrition, infections, sleep problems, and psychological issues. The feasibility of home dialysis therapies has been demonstrated in observational studies. As self‐care dialysis is often a challenge in the elderly patient, assisted intensive home HD may facilitate the long‐term continuation of this modality. Intensive nursing home HD seems to be an attractive goal for the future because many elderly ESRD patients reside in an extended care facility. Combination with rehabilitation and support by social worker and psychologist remains crucial in the holistic approach toward the elderly ESRD patient. Further studies are required to test the potential protective effects of intensive HD on functionality and quality of life in elderly ESRD patients, and to elucidate the mechanisms underlying frailty and other geriatric syndromes in this highly vulnerable patient population.     

The challenges of diabetes care in the dialysis unit

Nephrologists, dialysis facilities, and payers are confronted with a new and more difficult set of challenges to effectively care for the steadily increasing number of patients with diabetes mellitus (DM) developing end-stage renal disease (ESRD). U.S. Renal Data System (USRDS) data suggest that the current care of patients with DM on dialysis is suboptimal. Recently published reports have confirmed the value of HbA1C measurements in the diabetic dialysis population, that control of blood glucose lowers mortality, and that a program of care management and diabetes education can have a significant impact on patient outcomes. As leader of the nephrology team, the nephrologist should, at a minimum, be accountable for defining who is managing the diabetes. A more systematic and educated approach to DM and its complications needs to be developed by the renal community.     

In Quality We Trust; but Quality of Life or Quality of Care?

The ESRD program provides medical care to a diverse and medically complex patient population. The care for the ESRD patient population has become increasingly benchmarked with process of care measures. These measures include dialysis adequacy, anemia, nutrition, and vascular access outcomes. These process‐related dialysis measures may not improve the care of the individual patient as care relates to the individual's goals and values. There is also evidence that these process measures may not be causally related to quality of life, hospitalization, and survival. The adoption of patient‐reported outcomes may shift the balance toward more patient‐centered care. However, the extent to which mandated measures of health‐related quality of life and patient satisfaction result in improved outcomes remains unclear.     

PD First: Peritoneal Dialysis as the Default Transition to Dialysis Therapy

Peritoneal dialysis (PD) and in‐center hemodialysis (HD) are accepted as clinically equivalent dialysis modalities, yet in‐center HD is the predominant renal replacement therapy (RRT) modality offered to new end‐stage renal disease (ESRD) patients in the United States and most other industrialized nations. This predominance has little to do with clinical outcomes, patient choice, cost, or quality of life. It has been driven by ease of HD initiation, physician experience and training, inadequate pre‐ESRD patient education, ample in‐center HD capacity, and lack of adequate infrastructure for PD‐related care. As compared with in‐center HD, PD is a widely applicable, yet underutilized modality of RRT that provides comparable clinical outcomes, superior quality of life measures, significant cost savings, and many other unmeasured advantages. A “PD First” approach not only has advantages for patients but also physicians, healthcare systems, and society. In this review, we will summarize evidence demonstrating that PD should be the default modality when new ESRD patients are transitioning to dialysis therapy when preemptive transplantation is not an option and highlight the essential infrastructural requirements to allow for a “PD First” model.     

End-stage renal disease and the practice of nephrology

Data from a national survey of 336 nephrologists who provide dialysis care on capitation reimbursement show differences in practice activity associated with the proportion of patients with end-stage renal disease (ESRD). On the average, ESRD patients account for 53% of patients seen by these physicians. Nephrologists who have the majority of their visits with ESRD patients average more than 120 patient encounters per week, approximating the practice workloads of primary care physicians. Nephrologists spend comparable amounts of time providing treatment for ESRD and non-ESRD patients in the same settings, schedule additional office visits for facility dialysis patients, and provide treatment and advice for problems not related to dialysis. Whereas care for acute renal failure patients is primarily based on consultations and involves a narrow focus, treatment for ESRD involves the provision of comprehensive primary medical care by nephrologists to their patients being treated with dialysis.     

Renal replacement therapy in the elderly: medical, ethical, and psychosocial considerations

As patients over the age of 65 become the fastest growing segment of our treated end-stage renal disease (ESRD) population, nephrologists and allied healthcare workers who care for these patients must become well versed in the many issues specific to this group. Elderly patients contribute the greatest fraction to the incidence and prevalence of the United States ESRD population. Their life expectancy is greatly reduced compared with age-matched counterparts from the general population. Cardiac disease is the leading cause of death. Although renal transplantation remains the most successful form of renal replacement therapy, only a small fraction of elderly ESRD patients are transplanted. The renal research community has made great strides in improving patient outcomes on dialysis over the last decade in many areas; however, little attention has been focused on the elderly ESRD patient. The substantial mortality and comorbidity experienced by this population makes their management an ongoing challenge. Many unresolved issues remain for elderly ESRD patients in the timing of dialysis initiation, choice of dialytic therapy, use of renal transplantation, and management of cardiovascular disease. It is anticipated that future research in these areas will identify optimal treatment strategies for elderly ESRD patients starting on dialysis and improve patient outcomes.     

Dialysis for chronic renal failure: comorbidity and treatment differences by disease etiology

A national sample of dialysis physicians was used to obtain data for a comparison of patient characteristics, comorbid conditions and treatment patterns associated with the five leading causes of end-stage renal disease (ESRD). The data are used to assess trends in physician care for ESRD patients and likely changes in program costs. The analysis shows that patients with glomerulonephritis are the youngest. Those with hypertensive nephropathy are the oldest, and include the highest proportion of blacks, while those with polycystic kidney disease include the lowest proportion of blacks. Patients with diabetic nephropathy have the most problems noted at the time of physician contact, the most emergent and severe problems, the highest number of diagnostic tests utilized, the most complex treatments required and the longest physician time spent per encounter. Patients with 'other interstitial nephritis' are significantly more likely to have infections, musculoskeletal disorders, chronic obstructive pulmonary disease and neoplasms noted as comorbid conditions. They also have the highest number of therapeutic procedures and the greatest percentage of referrals for consultations. Survey data highlight the evolving nature of Medicare's ESRD program. With increasing numbers of elderly and diabetic patients, more physician time will be required for the overall care of the dialysis patient, and increasing costs associated with necessary diagnostic tests and referrals can be expected.     

Chronic kidney disease and cardiovascular disease in the Medicare population

BACKGROUND: The extent of diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) in the Medicare population is relatively unknown. Also unknown is the effect of these diseases on patient survival before end-stage renal disease (ESRD). METHODS: Prevalent cohorts of Medicare enrollees from 1996 to 2000 were assessed for diabetes and CKD, presence of CVD, and probability of death versus ESRD in the follow-up period. Hospitalization rates and, in diabetics, lipid testing and glycemic control monitoring were also assessed. RESULTS: The prevalence of diabetes in the Medicare population increased at 4.4% per year, reaching 18.9% in the 1999-2000 cohort. Approximately 726,000 elderly Medicare enrollees carry a diagnosis code for CKD. Those with CKD are 5 to 10 times more likely to die before reaching ESRD than the non-CKD group. In CKD patients, CVD is twice as common and advances at twice the rate. Cardiovascular disease advances at a similarly higher rate in CKD patients who die and those who survive to ESRD. Heart failure hospitalizations are 5 times greater in CKD patients and only 30% less than those in dialysis patients. Only half of the CKD patients with diabetes who advance to ESRD had a lipid or glycosylated hemoglobin test done in the year before or after dialysis initiation. CONCLUSION: Diabetes, the leading cause of ESRD, is increasing in the general Medicare population at 4.4% per year. Cardiovascular disease is common, progresses at twice the rate, is associated with death before ESRD, and patients receive suboptimal risk factor monitoring. Active identification and treatment of CKD patients is needed.     

Recent advances in pediatric dialysis: a review of selected articles

Important discoveries and studies that help inform us about the best methods to evaluate and manage children with end-stage renal disease (ESRD) continue to emerge. This review addresses a number of recent publications regarding important clinical issues for children with ESRD. Despite advances made in previous years, many clinical problems remain in the care of the pediatric dialysis patient. This review covers five topics of recent interest: three articles that address important patient outcome measures such as dialysis adequacy and hemoglobin; two articles that address growth failure in a chronic dialysis patients; five articles that address cardiovascular (CV) morbidity, mortality, and interventions to reduce CV risk in children; two articles that address mineral-bone disorder (MBD) and evidence that past strategies for MBD in children may have increased CV disease; and two articles that address nephrogenic systemic fibrosis, a recently described disorder in chronic kidney disease (CKD) patients that occurs in children as well as adults. Using a concise consistent format, each of the 14 key publications is summarized, and the "conclusion" for the practitioner is identified. The goal of this review is to highlight important work done in this area and focus attention on the important issues raised by each article.     

Epidemiology of Dietary Nutrient Intake in ESRD

Protein‐energy wasting (PEW) is one of the strongest risk factors of adverse outcomes in patients with chronic kidney disease including those with end‐stage renal disease (ESRD) who undergo maintenance dialysis treatment. One important determinant of PEW in this patient population is an inadequate amount of protein and energy intake. Compounding the problem are the many qualitative nutritional deficiencies that arise because of the altered dietary habits of dialysis patients. Many of these alterations are iatrogenically induced, and albeit well intentioned, they could induce unintended harmful effects. In order to determine the best possible diet in ESRD patients, one must first understand the complex interplay between the quantity and quality of nutrient intake in these patients, and their impact on relevant clinical outcomes. We review available studies examining the association of nutritional intake with clinical outcomes in ESRD, stressing the complicated and often difficult‐to‐study inter‐relationship between quantitative and qualitative aspects of nutrient intake in nutritional epidemiology. The currently recommended higher protein intake of 1.2 g/kg/day may be associated with a higher phosphorus and potassium burden and with worsening hyperphosphatemia and hyperkalemia, whereas dietary control of phosphorus and potassium by restricting protein intake may increase the risk of PEW. We assess the relevance of associative studies by examining the biologic plausibility of underlying mechanisms of action and emphasize areas in need of further research.     

Peritoneal dialysis in diabetic patients

Diabetes mellitus is the fastest growing cause of end-stage renal disease (ESRD) and has become the leading cause of such ESRD worldwide. In the United States, between 1984 and 1997, the proportion of new patients starting renal replacement therapies whose ESRD was caused by diabetes increased from 27% to 44.4%. Canada saw an increase from 16.5% in 1984 to 28.9% in 1997, and many European countries had similar increases. Among the modes of renal replacement, many clinicians have favored continuous ambulatory peritoneal dialysis (CAPD) for the treatment of diabetic ESRD for several reasons. Many studies have compared clinical outcomes in diabetic patients undergoing CAPD, and nondiabetic patients undergoing CAPD, or diabetic patients undergoing peritoneal dialysis (PD) and those undergoing hemodialysis (HD). However, only a small number of diabetic dialysis patients have been followed up for more than 5 years, largely because of the presence of several comorbid conditions at the start of dialysis and the coexistence of far-advanced target-organ damage at dialysis initiation and its progression during the course of dialysis. Diabetic patients undergoing PD and HD probably have similar survival, and those undergoing CAPD have lower survival and technique success rates than nondiabetic patients of comparable age. This article reviews the literature and our experience with diabetic patients undergoing PD and compares clinical outcomes in diabetic patients undergoing PD and HD.     

Long-term impact of chronic hemodialysis on glycemic control and serum lipids in insulin-treated type 2-diabetic patients

There are only a few data in the literature concerning metabolic control in insulin-treated diabetic patients with end stage renal disease (ESRD). The aim of the study was to find out the long-term impact of hemodialysis on glycemic control and lipid values in type 2 diabetic patients. Twenty insulin-treated type 2 diabetic patients (age 62 +/- 9 years, f:m=6:14) were evaluated. We compared HbAlc, fasting blood glucose (FBG), body weight, serum lipids, insulin requirement, and blood-pressure (BP) 12 and 6 months before dialysis, at the start of dialysis, and 6 as well as 12 months after the start. RESULTS: The mean HbA1c- and FBG-values were not significantly different before and after the start of dialysis therapy. The average insulin requirement was 26 +/- 10 IU/day in the predialysis period, 25 +/- 12 IU/day at the start, and 24 +/- 13 as well as 22 +/- 13 IU/day after the start of dialysis. The mean cholesterol level fell significantly from 199 +/- 63 and 190 +/- 49 mg/dL in the predialysis phase to 167 +/- 62 and 157 +/- 38 mg/dL after dialysis began. The triglyceride concentrations decreased only slightly after the start of dialysis. The incidence of hypoglycemia (n/patient/month) was markedly lower in the predialysis phase (0.4 vs. 0.6, NS) than after start of dialysis. In patients with residual diuresis (<500 mL urine/day) the needed insulin doses decreased significantly by 29% compared to patients with higher residual diuresis, whose insulin requirement remained unchanged. In summary, hemodialysis had no significant long-term effect on glycemic control in insulin-treated type 2 diabetic patients, but incidence of hypoglycemia tended to be higher under hemodialysis than in the predialysis period. Lipid levels tended to be lower after the initiation of dialysis therapy. Insulin requirement under hemodialysis decreased only in patients with loss of residual urine volume (below 500 mL urine/day).     

Renal cell carcinoma in patients with end‐stage renal disease: relationship between histological type and duration of dialysis

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To evaluate the clinical outcomes and histological types of renal cell carcinoma (RCC) arising in patients with end‐stage renal disease (ESRD), and to analyse the relationship of histopathological features with the duration of dialysis.

PATIENTS AND METHODS

Clinical characteristics and outcomes of 34 patients who had a radical nephrectomy for RCC arising in ESRD between November 1994 and June 2008 were investigated. Archive paraffin‐embedded tissue specimens obtained from 27 patients were histochemically and immunohistochemically analysed to determine the histopathological type.

RESULTS

There was one death from cancer and one patient with local progression within a median observation period of 29.5 months. Acquired cystic disease (ACD)‐associated RCC, clear cell‐papillary RCC, mucinous tubular and spindle‐cell carcinoma, and Xp11.2 translocation/TFE3 gene fusion were identified in eight, two, three and one patient, respectively. Conventional clear‐cell RCC was the predominant histological type (nine of 15) in patients with a duration of dialysis of <10 years, while ACD‐associated RCC was predominant (seven of 12) in those with dialysis for ≥10 years. Sarcomatoid foci were identified in three patients with dialysis for ≥10 years. Papillary adenoma was microscopically identified as a satellite tumour in 10 patients.

CONCLUSION

The spectrum of histological types of RCCs arising in ESRD is distinct from that of sporadic RCCs. Patients with a longer duration of dialysis should have particular attention for progression and metastasis. Immunohistochemical profiling is efficient in the histological classification of RCCs arising in ESRD, although knowledge about genetic changes remains to be accumulated.     

Prevention of renal failure: the Malaysian experience

Renal replacement therapy in Malaysia has shown exponential growth since 1990. The dialysis acceptance rate for 2003 was 80 per million population, prevalence 391 per million population. There are now more than 10,000 patients on dialysis. This growth is proportional to the growth in gross domestic product (GDP). Improvement in nephrology and urology services with widespread availability of ultrasonography and renal pathology has improved care of renal patients. Proper management of renal stone disease, lupus nephritis, and acute renal failure has decreased these as causes of end-stage renal disease (ESRD) in younger age groups. Older patients are being accepted for dialysis, and 51% of new patients on dialysis were diabetic in 2003. The prevalence of diabetes is rising in the country (presently 7%); glycemic control of such patients is suboptimal. Thirty-three percent of adult Malaysians are hypertensive and blood pressure control is poor (6%). There is a national coordinating committee to oversee the control of diabetes and hypertension in the country. Primary care clinics have been provided with kits to detect microalbuminuria, and ACE inhibitors for the treatment of hypertension and diabetic nephropathy. Prevention of renal failure workshops targeted at primary care doctors have been launched, opportunistic screening at health clinics is being carried out, and public education targeting high-risk groups is ongoing. The challenge in Malaysia is to stem the rising tide of diabetic ESRD.