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Query: UMLS:C0011881 (diabetic nephropathy)
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Since its experimental introduction in 1960, hemodialysis has become a widely performed and relatively safe procedure. Therapeutic strategies have been developed, and the numbers of long-term survivors of hemodialysis therapy have been increasing. Hemodialysis therapy was introduced at Sangenjaya Hospital in October 1970, and the 16 patients who have survived for more than 30 years on hemodialysis therapy since its introduction at the hospital were enrolled in this study to investigate the characteristics of long-term hemodialysis patients. For comparison, 50 patients on hemodialysis for less than 30 years were also studied (21 patients with <10 years hemodialysis, 13 with 10-20 years hemodialysis and 16 with 20-30 years hemodialysis). Background information (age, gender, and cause of renal disease), dialysis dose (single pool [sp.] Kt/V), mineral metabolism (serum phosphate), anemia management (serum hemoglobin), and nutrition (serum albumin and reduced interdialytic weight gain) were assessed. Hemodialysis was instituted at 28.7 +/- 6.4 years of age. The primary cause of end-stage renal disease was chronic glomerulonephritis in all of the patients except one, and in that patient it was polycystic kidney disease. As an index of the dialysis dose, sp. Kt/V was 1.2 +/- 0.11. As an index of mineral metabolism, serum phosphate was 5.4 +/- 0.9 mg/dL. As an index of anemia management, serum hemoglobin was 10.2 +/- 1.2 g/dL. As indexes of nutrition, serum albumin was 4.0 +/- 0.2 g/dL and interdialytic weight gain was 4.43 +/- 1.36%. The sp. Kt/V-value, serum phosphate, serum hemoglobin and interdialytic weight gain did not differ between the four different hemodialysis duration groups. Serum albumin was lower in the >30 group (4.0 +/- 0.2 g/dL) than in the <10 group (4.2 +/- 0.3 g/dL) (P = 0.046). As the duration of hemodialysis has increased, the age at hemodialysis induction has become younger. The cause of the renal failure was chronic glomerulonephritis in most of the cases. None had diabetic nephropathy. Improvement of the prognosis of patients with diabetic nephropathy is required. Most of the indexes of these patients nearly satisfied the recommended values.
Ther Apher Dial 2007 Aug
PMID:Characteristics of patients on hemodialysis therapy for more than 30 years. 1766 33

In 2005, the acceptance rate for renal replacement therapy (RRT) in adults in the UK was 108 per million population (pmp). This was derived from complete data for adults in the UK, as data were obtained separately from the five English renal units not currently returning to the Registry. In addition, 87 children started RRT (see Chapter 13) giving a total incidence of 110 pmp. From 2001 to 2005 there has been an 7.3% rise in the acceptance numbers in those 42 renal units with full reporting throughout that period. In the UK, for adults in 2005, the crude acceptance rates in Local Authorities (LA) varied from 0 (in two very small LA areas in Scotland and Northern Ireland) to 271 pmp; the standardized rate ratios for acceptance varied from 0 to 2.76. Excluding the two areas with null returns, 20 areas had significantly low ratios, all of them in England. Thirty had significantly high ratios, seven in Northern Ireland, four in Scotland, three in Wales and seven in London. Over the period 2001-2005, 25 areas had a significantly low standardized acceptance rate; 24 in England and one in Scotland. All except one of these had ethnic minority populations of <10%. Thirty-seven had high standardized acceptance rates, seven in Scotland where ethnicity data were not available, 14 from areas with ethnic minority populations in excess of 10%, and 12 were in Wales or the Southwest of England. The median age of patients starting RRT in England has increased from 63.8 years in 1998 to 65.2 years in 2005. The median age of incident non-White patients is significantly lower at 56.8 years. In England, the acceptance rate is highest in the 75-79 age band at 408 pmp, as in Scotland at 580 pmp; in Wales the peak is in the 80-84 age band at 525 pmp, as in Northern Ireland with a rate of 825 pmp. Diabetic renal disease (20%) remains the most common specific primary renal disease. There was a significant positive correlation between the percentage of incident RRT patients with diabetic renal disease and the percentage of non-Whites in the incident cohort. Haemodialysis (HD) was the first modality of RRT in 76% of patients, peritoneal dialysis (PD) in 21% and pre-emptive transplant in 3%. In 1998, the proportion whose first modality was HD was 58% and this continues to increase. By day 90, 8% had died, a further 1% had stopped treatment or been transferred out leaving 91% of the original cohort on RRT. Of these, 71% were on HD, 26% on PD and 3% had received a transplant. Data on first referral to a nephrologist were available from 22 centres for the period 2000-2005 (for a total of 5611 patients and 59 centre-years). In 2005, the mean percentage of patients referred late (<90 days before dialysis initiation) was 30% (centre range 13-48%). This was similar to the value in 2000. Patients referred late were older, a higher proportion of them were male, a lower proportion non-White, and a lower proportion with no recorded comorbidity. Patients with polycystic kidney disease and diabetic nephropathy tended to be referred early compared with the whole incident cohort and those with uncertain aetiology and no recorded diagnosis referred late. Estimated GFR (eGFR) at the start of RRT appears to be higher in older than younger patients. eGFR is significantly lower in those referred late compared with those referred earlier and this is especially marked in the older patients. The geometric mean eGFR of all patients starting RRT rose from 6 in 1997 to above 7.5 in 2003, since when it has remained stable.
Nephrol Dial Transplant 2007 Aug
PMID:New adult patients starting renal replacement therapy in the UK in 2005 (chapter 3). 1772 40

The influence of the type of dialysis on survival of patients with end-stage renal disease (ESRD) is controversial. To compare survival among patients with ESRD receiving peritoneal dialysis (PD) or hemodialysis (HD), we conducted a prospective cohort study in a single center from April 1995 to March 2005. During that period, 454 patients (161 women, 293 men; mean age: 61.7 +/- 14.4 years; 46.6% with diabetic nephropathy) were started on HD therapy, and 120 patients (40 women, 80 men; mean age: 54.5 +/- 11.3 years; 16.7% with diabetic nephropathy) were started on PD therapy; all patients were followed for at least 3 years. The 3-year survival rates were 65% for the HD patients and 81% for the PD patients (p < 0.05). The causes of death in patients undergoing HD were 52% cardiovascular 25% infectious diseases, and 12% cancer; in patients undergoing PD, the causes were 36% infectious diseases, 24% cardiovascular, and 6% cancer Median time from initiation of dialysis to study enrollment was 90 days for HD patients and 180 days for PD patients. Although patients in this study were not randomly assigned to their initial type of dialysis therapy, survival rate was found to be dependent on dialysis type. Moreover, this study suggests the importance of early referral and evaluation of risk factors in individual patients before they are started on dialysis therapy.
Adv Perit Dial 2007
PMID:Comparison and survival of patients receiving hemodialysis and peritoneal dialysis in a single center. 1788 22

The treatment according to the Japanese Society for Dialysis Therapy guidelines was performed in 189 patients on maintenance dialysis in our clinic. The mean age of the patients was 64.9 years and the mean dialysis period was 6.3 years. The underlying disease was diabetic nephropathy in 40.7% of the patients, chronic glomerulonephritis in 30.2%, and nephrosclerosis in 13.8%. In May 2006 before the use of JSDT guidelines, patients with phosphorus and calcium concentrations in the control goal range were most frequently observed (69.8%), followed in order by those with a high concentration of phosphorus alone (13.8%), those with a low concentration of phosphorus alone (2.6%), those with a high concentration of calcium alone (10.1%), those with high concentration of both phosphorus and calcium (3.7%). Treatment according to JSDT guidelines was performed for 6 months in these patients. In January 2007, the group with both phosphorus and calcium concentrations in the goal range accounted for 82.2%, showing improvement. The intact PTH concentration in patients with normal phosphorus and calcium concentration was in the reference range (60-180 pg/ml) in about 50% of the patients, high (>180 pg/ml) in 35%, low (<60 pg/ml) in 10% during the study periods. The intact PTH concentration was often about 40 pg/ml in patients with a concentration <60 pg/ml, 120 pg/ml in those with a concentration of 60-180 pg/ml, and 200-250 pg/ml in those with a concentration >180 pg/ml. The concentration of NTx was significantly higher in the patients with an intact PTH concentration >180 pg/ml than in those with a concentration of <60 pg/ml or those with a concentration of 60-180 pg/ml and significantly increased with time.
Ther Apher Dial 2007 Oct
PMID:Attainment of the Japanese Society for Dialysis Therapy guidelines for the management of secondary hyperparathyroidism in chronic hemodialysis patients in our clinic. 1797 86

The activity of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of diabetic nephropathy. However, the effect of angiotensin-converting enzyme (ACE) inhibition on the RAAS appears to be modulated by a number of factors including the I/D polymorphism of the ACE genotype. In this study, we attempted to find independent correlates of ACE activity in 121 macroalbuminuric type 2 diabetic Iranian patients under chronic ACE inhibition. Both univariate and multivariate analyses were used. The presence of the D allele was independently associated with significantly higher levels of ACE activity (with the II genotype as reference, P < 0.001, B = 27.3, 95% CI = 17.6-37.1), and this association was not eliminated by potentially confounding variables. In conclusion, the D allele is a significant independent correlate of ACE activity in macroalbuminuric type 2 diabetic Iranian patients under long-term ACE inhibition.
Nephrol Dial Transplant 2008 Apr
PMID:Correlates of ACE activity in macroalbuminuric type 2 diabetic patients treated with chronic ACE inhibition. 1798 76

Phenomenal growth in continuous ambulatory peritoneal dialysis (CAPD) has occurred in the developing countries of Asia. In many regions in Asia, neither governments nor insurance companies fully cover treatment expenses for dialysis. Hence, patients in developing countries such as India, Bangladesh, Pakistan, and Nepal use just three 2-L exchanges daily. Typical practice in many centers is to do daytime CAPD with a dry night. Most of our Indian patients who are on three exchanges per day showed a Kt/V of 1.67 and 2-year survival rate of 60% with a normalized protein equivalent of nitrogen appearance of 0.73 - 0.80 g/kg daily. Vegetarians had a lower protein consumption rate and lower serum albumin levels. Peritoneal membrane characteristics vary among high, high average, and low average in various regions of Asia. The prevalence of diabetic nephropathy, with its associated comorbid conditions, as a major cause of end-stage renal disease in the Indian subcontinent explains the differences in the CAPD mortality rates between India and various Asian countries. Given the financial constraints in countries in Asia, small-volume dialysis of 6 L daily may be an acceptable compromise in some patient populations with a smaller body size and significant residual renal function; however, dialysis dose should be individualized according to the needs of each patient.
Perit Dial Int 2003 Dec
PMID:Are three exchanges suitable for Asian patients on peritoneal dialysis? 1798 56

It is supposed that some stress-induced heat shock proteins (Hsps) are regulated through e.g. stimulation of the p38MAPK/MK(MAPKAP)-2 signalling pathway. It has been postulated from in vitro experiments that phosphorylation of Hsp25(rodents)/Hsp27(human), the major phosphorylation substrate of MK2, is responsible for mesangial contractility and glomerular hyperfiltration in the diabetic kidney. To verify this hypothesis in vivo we studied the renal function of nondiabetic and streptozotocin (STZ)-induced, diabetic MK2(-/-) mice in comparison to wild-type (WT) control mice. Following 8 weeks of hyperglycaemia, light microscopy showed increased glomerulosclerosis and tubulointerstitial renal fibrosis in both diabetic study groups. Protein analysis demonstrated that Hsp25 phosphorylation is stimulated upon high-glucose condition but inhibited in the diabetic MK2(-/-) mice. However, we found the kidney-body weight ratio significantly increased in diabetic WT and MK2(-/-) mice. No difference regarding the increased expression of the extracellular matrix proteins and TGF-beta1 between both diabetic study groups was observed. Importantly, diabetic MK2(-/-) mice showed no protection against renal hyperfiltration in the diabetic state and the development of diabetic albuminuria. Although activation of p38MAPK has been previously shown in diabetes mellitus, our results indicate that blockade of the downstream MK2/Hsp25 signalling pathway does not interfere with the development of early diabetic nephropathy.
Nephrol Dial Transplant 2008 Jun
PMID:Deletion of MK2 signalling in vivo inhibits small Hsp phosphorylation but not diabetic nephropathy. 1818 4

Tubulo-interstitial pathology in diabetic nephropathy is thought to be caused by cell injury that is induced by high ambient glucose levels and increased proportions of glycated proteins. Other mechanistic hypotheses engage glomerular ultrafiltration of proteins and bioactive growth factors and their effects on tubular cells. Some scholars promote tubular ischaemia due to reduced peritubular blood flow as a response to glomerular injury. All of these mechanisms contribute to renal tubulo-interstitial injury in diabetic nephropathy. However, they do not well explain observations that have been made in studies of experimental animals and evaluations of human biopsies showing dilated collecting ducts in early diabetic nephropathy. Dilatation of distal nephron segments is routinely seen in human biopsies or in histological sections from experimental diabetic nephropathy and is reminiscent of similar findings in obstructive nephropathy. Moreover, it is these dilated tubules that are the primary source for pro-inflammatory and pro-fibrogenic cytokines and regulators. Based on this large body of observations from this laboratory and the published literature this narrative develops a novel hypothesis where hyperglycaemic, osmotic polyuria play important contributory roles in the initiation and progression of tubulo-interstitial injury in diabetic nephropathy.
Nephrol Dial Transplant 2008 Jul
PMID:Osmotic polyuria: an overlooked mechanism in diabetic nephropathy. 1845 80

Of a large body of literature reporting clinical outcomes for patients maintained on peritoneal dialysis (PD), most publications have focused on relatively short-term results. Few reports have focused on long-term survival in PD patients. Here, we present our experience with long-term patient outcomes and further analyses of the trends in demographics and clinical outcomes of 2301 end-stage renal disease (ESRD) patients treated with continuous ambulatory PD (CAPD) during a 25-year period (1981 - 2005) at our institute. Outcomes were analyzed for 1656 patients, excluding those younger than 15 years of age at initiation of CAPD, those having less than 3 months' follow-up, or those who had been on hemodialysis or who received a kidney graft before starting CAPD. In the study patients, technique survival at 5 and 10 years was 71.9% and 48.1% respectively. Patient survival was 69.8% and 51.8%. Mean age at the start of PD (50.4 +/- 13.9 years vs. 44.2 +/- 13.9 years, p < 0.01), ESRD incidence as a result of diabetic nephropathy (30.5% vs. 19.5%, p < 0.01), and incidence of cardiovascular comorbidities (26.6% vs. 20.5%, p < 0.01) were all significantly greater in patients who started PD during the second half of the study period (1993 - 2005) as compared with the first half (1981 - 1992). A multivariate analysis adjusting for these changes in demographics and comorbid conditions revealed that PD therapy starting in 1993 - 2005 was associated with a significant reduction in technique failure [hazard ratio (HR): 0.65; p < 0.01] and mortality (HR: 0.68; p < 0.01) as compared with the earlier period. However, in subgroup analyses, technique survival was not observed to be significantly improved in patients with diabetes. In summary, technique and patient survival have significantly improved despite increases in patient age, cardiovascular comorbidity, and ESRD caused by diabetes. Although diabetes, older age, and cardiovascular comorbidities are not factors that are easily modifiable to improve PD outcomes, results at our institution are encouraging in an era of declining PD utilization.
Perit Dial Int 2008 Jun
PMID:Long-term clinical outcomes of peritoneal dialysis patients: single center experience from Korea. 1855 58

A statistical survey of dialysis patients for the year 2006 was carried out for 4051 medical facilities across Japan, and responses were received from 3985 (98.37%) facilities. There were 264 473 dialysis patients (including 9003 peritoneal dialysis patients) in Japan at the end of 2006, which showed an increase of 6708 (2.6%) from the end of 2005. The number of patients per million population was 2069.9. The crude mortality rate during 2006 was 9.2%. The mean age of the patients who began dialysis (in 2006) was 66.4 years, and the mean age of the entire dialysis population was 64.4 years. The primary renal diseases of the patients who began dialysis were diabetic nephropathy (42.9%), chronic glomerulonephritis (25.6%), and nephrosclerosis (9.4%). Of the 3488 facilities that participated in the survey on the dialysate water quality, 2873 facilities (82.4%) measured the endotoxin concentration in the dialysate; and 1197 facilities (37.1%) out of 3228 measured the bacterial count in the dialysate. The mean hemoglobin concentration in the dialysis population at the end of 2006 was 10.23 +/- 1.33 g/dL, which was equal to that at the end of 2005 (10.23 +/- 1.37 g/dL). The mean concentration of serum creatinine in 15 853 patients who started dialysis during 2006 was 8.37 +/- 3.58 mg/dL. The estimated glomerular filtration rate, which was calculated with formula modified for the Japanese population from the Modification of Diet in Renal Disease (MDRD) Study equation, was 5.46 +/- 6.60 mL/min/1.73 m(2).
Ther Apher Dial 2008 Dec
PMID:Overview of regular dialysis treatment in Japan as of 31 December 2006. 1914 Aug 42


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