Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure: results of the ANNE study

It was found that in Belgium, renal imaging techniques, demonstratinga decreased renal mass of both kidneys combined with eitherbumpy contours or papillary calcifications, were the only methodsto reliably diagnose analgesic nephropathy (AN) in patientswith end-stage renal failure. However, these criteria were selectedin an area with a high prevalence of this disease (15.6% ofthe dialysis population at December 1990). To evaluate the criteriaselected to diagnose AN in populations with lower or unknownprevalences of AN, the Analgesic Nephropathy Network of Europe(ANNE) was formed, consisting of 23 dialysis units from 14 Europeancountries and Brazil. During 1991–1992, 598 new patientswith equivocal diagnosis of renal disease (excluding biopsy-provenglomerulonephritis, polycystic disease, diabetic nephropathyand other systemic diseases) and who began renal replacementtherapy in the ANNE centres were evaluated by a short questionnaireand two renal imaging techniques: sonography and either tomographyor computed tomography (CT) scan. A comparison of 82 abusers(daily use of analgesic mixtures for at least 5 years) and 495controls corroborated the excellent diagnostic performance ofthe renal imaging techniques for AN. We recommend the use ofthese renal imaging criteria in all patients without a clearrenal diagnosis in order to obtain a more reliable insight intothe magnitude of the AN problem in different countries.     

Incidence of analgesic nephropathy among patients undergoing renal replacement therapy in Czech republic and Slovak republic

BACKGROUND.: The occurrence of analgesic nephropathy (AN) among renal replacementtherapy patients in former Czechoslovakia is not known. Previoussurveys were not based on representative samples and lackeduniform criteria for diagnosing the disease. METHODS.: Incidence of AN in former Czechoslovakia was investigated inpatients commencing renal replacement therapy in 24 (1/3 ofall) dialysis centres from 1 January to 31 December 1992. Patientsshowing an unclear renal diagnosis (n=149) were investigatedwith an interview and renal imaging techniques. The diagnosisof AN was withheld or rejected on the base of recently publisheddiagnostic criteria demonstrating that a decreased renal massof both kidneys combined with bumpy contours and/or papillarycalcifications had a high performance for diagnosing AN (NephrolDial Transplant 1992; 7: 479–486). RESULTS.: Based on the renal imaging criteria, AN was diagnosed in 30of 328 registered patients, resulting in an AN incidence of9.1% while the EDTA data only mentioned an incidence of 4.8%(period 1986–1989). The products most commonly abusedwere analgesic mixtures containing two analgesic substancescombined with caffeine and/or codeine. CONCLUSIONS.: AN was found to be a common disease in the Czech and SlovakRepublics. The disease was diagnosed using reliable renal imagingcriteria.     

Incidence of analgesic nephropathy in Berlin since 1983.

BACKGROUND: Phenacetin was removed from the German market in 1986 and was replaced mainly in analgesic compounds by acetaminophen. Our objective was to examine the effect of this measure on the incidence of analgesic nephropathy in light of the changes in other end-stage renal diseases. METHODS: We therefore compared the proportion of renal diseases in all patients starting dialysis treatment during three 18-month periods: 4/1982-9/1983 (n=57); 1/1991-6/1992 (n=81); and 10/1995-3/1997 (n=76). RESULTS: On the one hand, the proportion of end-stage analgesic nephropathy decreased significantly from 30% in 1981-1982 to 21% in 1991-1992 and 12% in 1995-1997 (P=0.01). On the other hand, type II diabetes increased significantly from 7% to 22% (P=0.01) and 29%, (P=0.001). Using the chi2 distribution test to analyze the frequencies of seven diseases at three different time intervals, however, showed that the changes in renal-disease proportions between 1982-1983, 1991-1992 and 1995-1997 were not significantly independent. There was a significant median age increase from 52 years (CI0.95 44-58) in 1982-1983 to 63 (CI0.95 55-67) in 1991-1992 and 63 (CI0.95 60-66) in 1995-1997 (P=0.003) for all patients starting dialysis but not for those with analgesic nephropathy [59 (55-71) vs 64 (53-67) and 61 (50-72); n.s.]. CONCLUSION: The decrease of end-stage analgesic nephropathy since 1983 may be partially due to the removal of phenacetin from the German market in 1986. However, considering the general increase in numbers of dialysis patients, their higher age and the increased incidence of type II diabetes, the decrease in analgesic nephropathy is not a statistically significant independent variable. Altered admittance policies for dialysis treatment have yielded a new pattern of renal-disease proportion which interferes with changes in the incidence of analgesic nephropathy.     

Diabetic muscle infarction in end-stage renal disease.

BACKGROUND: Diabetic muscle infarction (DMI) is an unusual disorder of type 1 and type 2 diabetic patients with advanced microvascular damage including nephropathy. Few reports describe this complication among dialysis patients. METHODS: We studied four patients with terminal renal failure due to diabetic nephropathy who developed isolated skeletal muscle infarction at our institution between January 1998 and January 2003, and reviewed 15 additional cases of DMI reported among dialysis patients (Medline database search). RESULTS: Analysis of available data for all 19 cases revealed the following features: mean age at symptom onset of 46.4 years; average duration of renal replacement 25.7 months (range 36 h to 72 months); male predominance (2.2:1); higher prevalence of type 2 vs type 1 diabetes (2.2:1); and more common use of haemodialysis than peritoneal dialysis (2.6:1). One patient developed symptoms after being immobilized during surgery and initiating dialysis. Thigh involvement was frequent (17/19). Fever, leucocytosis and elevated serum creatine kinase levels were noted inconsistently, but were seen commonly with early evaluation after symptom onset. Erythrocyte-sedimentation rate and C-reactive protein levels were high when checked. All 16 instances of magnetic resonance imaging (MRI) demonstrated increased T2-weighted signal from affected muscles. Seven patients were managed without muscle biopsy. Histological features included myofibre necrosis (8/12), inflammatory infiltrates (8/12) and microvasculopathy (6/12). Symptoms resolved with conservative therapy, but patients were at high risk for subsequent infarctions of other muscles (14/19). CONCLUSIONS: DMI should be suspected in any diabetic dialysis patient who develops a painful, swollen muscle. A conservative MRI-based diagnostic approach may lead to satisfactory outcomes. The pathogenesis of the disorder is controversial, but the clinical sequence of one of our cases suggests precipitation by immobilization, direct pressure and/or haemoconcentration.     

Is Analgesic Nephropathy Still a Problem in Belgium?

End-stage renal failure due to analgesic nephropathy still frequentlyoccurs in Belgium. In a study conducted at the end of 1984 including53 of the 54 dialysis centres, a prevalence of analgesic nephropathyin dialysis patients of 17.9% was found. The epicentre of thedisease was situated in a small area in the northern part ofthe country, the southern part showed a clearly lower prevalence. The annual consumption of analgesic preparations in 1983 wasapproximatively 25 g per capita, in the north as well as inthe south. In the north analgesic mixtures in powder form hadan important market share in some particular areas, where theprevalence of end-stage renal failure due to analgesic nephropathyis the greatest. A general population survey (n=855) showed that 83% of subjectshad analgesic medications at home. Abuse of these drugs wasfound in 2.1% of the studied population. Abusers were mainlyfemales most commonly taking analgesic mixtures.     

Diagnostic criteria of analgesic nephropathy in patients with end-stage renal failure: results of the Belgian study.

Diagnostic criteria of analgesic nephropathy with well-defined sensitivity and specificity are not available. During a 2-year period all new patients (n = 273) starting renal replacement therapy in 13 Belgian dialysis units were investigated aiming to select diagnostic criteria of analgesic nephropathy with acceptable performance. Using several interview techniques, a history of analgesic abuse was found in 31% of the patients. Analgesic abusers presenting a clear non-analgesic-related renal diagnosis were excluded from analysis (n = 25). Comparing the remaining abusers (n = 60) and patients without a history of analgesic abuse (n = 188) it was found that renal imaging investigations (sonography plus tomography), showing a decrease in length combined with bumpy contours of both kidneys, presented a sensitivity of 90% and a specificity of 95%. The additional finding of signs of renal papillary necrosis resulted in an overall sensitivity of 72% and a specificity of 97%, giving a positive predictive value of 92%. Other signs frequently mentioned in the literature (hypertension, anaemia, sterile pyuria, bacteriuria, proteinuria) showed insufficient sensitivity and/or specificity to be of help for diagnosing analgesic nephropathy in end-stage renal failure (ESRF) patients starting renal replacement therapy.     

Ultrasonic findings in analgesic nephropathy

34 patients with analgesic nephropathy (AN) were investigated by real-time ultrasonography. In 11 out of 14 patients on maintenance dialysis and in 16 out of 20 patients with renal insufficiency calcified renal papillae were documented surrounding the central sinus in a typical garland pattern. Moreover, by surveying a group of patients with renal insufficiency of unknown origin, AN was assumed in 10 patients and was then confirmed by a hitherto unknown history of analgesic abuse as well as by laboratory findings. In 37 patients radiologic or autopsy data were additionally available. A close correlation to the scanning pattern was found in 31 of these patients. In 30 healthy volunteers and 56 patients with renal insufficiency due to chronic glomerulonephritis (n = 24) or diabetic nephropathy (n = 32) calcified renal papillae were found only in 1 case. 5 out of 20 patients on maintenance dialysis due to other diseases than AN showed renal calcifications forming an approximate garland arrangement. In these patients sonography may therefore indicate AN only in very characteristic cases. We believe that renal papillary calcifications surrounding the central sinus in a garland pattern may indicate AN in most cases and thus may be helpful in establishing the diagnosis of AN.     

Renal replacement therapy in the Canary Islands: demographic and survival analysis

BACKGROUND: The continuous increase in the number of patients on renal replacement therapy (RRT) has heightened the importance of renal patient registries to respond to the demand for data on the state of health, quality and cost of care provided for these patients. Our aim was to analyze the epidemiological profile of this population in the Canary Islands. METHODS: All patients on RRT between January 1999 and December 2003 were considered in this analysis. The information was obtained from the database of the Canary Registry of Renal Patients. RESULTS: We observed a continuous increase in incidence throughout the study period (from 138 per million population (pmp) in 1999 to 160 pmp in 2003), being more evident in patients >65 yrs. Prevalence followed a similar course, increasing from 875 to 972 pmp, being especially evident in the 65-74 yr age group. An alarming finding was the high incidence (43.5%) and prevalence (37.5%) of diabetic nephropathy. While the proportion of hemodialysis (HD) or transplant patients increased, that of peritoneal dialysis (PD) remained low and stable (prevalence of 5% in 2003). Almost half the RRT patients had functioning grafts, with a notably high rate of 58 transplants pmp in 2003, and a prevalence of 425 pmp. Age (hazard ratio (HR) [95% confidence interval (95% CI)] 1.04 [1.03-1.05]; p < 0.001) and diabetic nephropathy (1.47 [1.19-1.82]; p < 0.001) were independently associated with mortality in dialysis patients. Those returning to dialysis after graft loss had a 69% greater risk of death than incident dialysis patients (1.69 [1.06-2.69]; p = 0.026). Cardiovascular events were the main cause of death in all dialysis modalities. Patient death was the main cause of graft loss. CONCLUSIONS: The most outstanding finding was the high incidence and prevalence of patients on RRT, mainly due to diabetic nephropathy. Renal transplant rates were among the highest reported in renal patient registries.     

Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis

PURPOSE: We verified differences in the incidence, clinical characteristics and outcomes between patients on chronic dialysis for end stage renal disease with renal cell carcinoma (RCC) and those with transitional cell carcinoma (TCC). MATERIALS AND METHODS: Data regarding RCC and TCC were reviewed in the medical records of 6,201 patients with end stage renal disease who underwent chronic dialysis between January 1990 and June 2003 in our 38 affiliated dialysis centers, and data were compared with those reported in Australia and New Zealand. RESULTS: Among the patients RCC developed in 38 (0.61%) and TCC developed in 16 (0.26%) during maintenance dialysis. The primary renal disease was chronic glomerulonephritis in patients with RCC (68.4%) and diabetic nephropathy in patients with TCC (43.8%, p = 0.002). Mean patient age at initiation of dialysis was 45 years for those with RCC and 63 for those with TCC (p < 0.001). Mean interval from dialysis induction to tumor diagnosis was 143 months for patients with RCC and 54 months for patients with TCC (p < 0.001). Of 38 RCCs 23 (60.5%) were incidentally detected by regular abdominal imaging examinations while painless gross hematuria was the cardinal symptom in 13 (81.2%) of 16 TCCs. Overall and cancer specific survivals after tumor diagnosis were significantly superior in patients with RCC compared to those with TCC (p = 0.0001 and p = 0.0003, respectively), and the cancer specific 5-year survival was 88.9% for RCC and 29.5% for TCC. In both cancers tumor stage significantly increased the risk of cancer specific death. Compared with patients from Australia and New Zealand, the incidence of RCC was higher and that of TCC was lower in our patients (p <0.001). CONCLUSIONS: In the Japanese population on dialysis RCC is more common than TCC. Since long-term dialysis is a risk factor for RCC, regular imaging examinations may have contributed to the favorable outcome of our patients on dialysis with RCC. In contrast, the unfavorable outcome of TCC suggests the need for effective diagnostic measures for early detection of TCC in patients on dialysis.     

The 1998 report of the Japanese National Registry data on pediatric end-stage renal disease patients

We carried out a nationwide survey on patients less than 20 years of age with pediatric chronic end-stage renal disease (ESRD) in Japan for the year 1998. There were 582 patients who had started on renal replacement therapy before 1998, and 105 patients who had been newly introduced to renal replacement therapy in that year. The prevalence rate of the ESRD patients already on treatment was 22 per million population (aged 0–19 years) in 1998. Older patients had a higher prevalence rate than younger ones. There were 345 patients on dialysis as of 1 January 1998, and 237 patients with transplants. The major diseases causing ESRD were renal hypoplasia/dysplasia and focal segmental glomerulosclerosis. Of the 237 patients (46.9%) who had received renal transplants before 1 January 1998, 262 patients (96%) received their transplants from living kidney donors. The incidence rate for the new ESRD patients was 4 per million population (aged 0–19 years) in 1998. Older patients had a slightly higher incidence rate than younger ones. Peritoneal dialysis was used more frequently than hemodialysis under 15 years (85%–95% and 39% respec-tively), especially in very young patients. The major diseases causing ESRD were the same as in the patients already on treatment. The transplant rate for the year 1998 was 10 per 100 dialysis patient-years (patients aged 0–19 years) with 9 living kidney donors. The death rate was 15.6 per 1,000 dialysis patient-years (patients aged 0–19 years); the major causes of death being cardiovascular diseases and infections. Received: 30 January 2001 / Revised: 3 January 2002 / Accepted: 4 January 2002     

Paracetamol: a cause for analgesic nephropathy and end-stage renal disease

180 patients with end-stage renal disease (ESRD) on maintenance dialysis and those who had undergone renal transplantation were questioned retrospectively. 14 patients had consumed excessive quantities of analgesics (greater than 1 kg) prior to the institution of long-term dialysis or transplantation. Sonographic examination done on these patients indicated that 7 had renal papillary necrosis (RPN). The sonographic features were renal papillary calcifications surrounding the central sinus in a complete or incomplete garland pattern. In 5 of these patients RPN is attibutable to the excessive consumption of paracetamol. We have earlier reported 10 cases of RPN due to excessive consumption of paracetamol. Thus 15 cases of RPN attributable to paracetamol consumption (1.0-15.3 kg over a period ranging from 3 to 23 years) have been documented. It is concluded that paracetamol may assume an increasingly important role in the causation of analgesic nephropathy (AN) and ESRD.     

Denovo urothelial carcinoma of the upper and lower urinary tract in kidney — transplant patients with end-stage analgesic nephropathy

Summary Patients with end-stage analgesic nephropathy bear a higher risk for urothelial cancer than do patients with other renal diseases. In a retrospective study in patients with analgesic nephropathy and kidney transplants we analyzed the prevalence and clinical course of de novo urothelial cancer. Diagnosis of analgesic nephropathy was based on the patients' history and clinical data. Only patients under cyclosporine treatment were included. Between 1968 and 1993, 2,371 kidney transplants were performed on 2,072 patients in the Department of Abdominal and Transplant Surgery. The prevalence of analgesic nephropathy was 3.1%. Of 65 patients with analgesic nephropathy and kidney transplants, 10 (15.4%) developed urothelial carcinoma; 10.8%, bladder cancer; and 9.1%, renal pelvic cancer. The mean age at diagnosis was 56.1 years. Urothelial cancer occurred on average at 33.6 months posttransplantation. On average, 6 of 10 patients with urothelial cancer died of the disease at 16.9 months after the diagnosis. All patients with urothelial bladder cancer had a muscle-infiltrating tumor of moderate or high grade. Since urothelial renal pelvic cancer occurred in 9.1% of our patients with analgesic nephropathy and urological screening is insufficient in patients on dialysis, we suggest that prophylactic nephroureterectomy be performed on one side before transplantation and on the contralateral side at 3–6 months after transplantation. An aggressive approach is indicated in patients with urothelial cancer of the bladder.     

Urine cytology as a screening method for transitional-cell carcinoma in dialysis patients with analgesic nephropathy

The abuse of analgesic-containing drugs leads to chronic nephropathy with an increased risk of developing a transitional-cell carcinoma of the urinary tract. In our experience follow-up is often stopped or has never been started when patients present for dialysis. We use urine cytology as the screening method. Nine of the 138 patients entering dialysis between 1980 and 1990 had analgesic nephropathy. In three patients urine cytology led to a suspicion of malignancy. Cystoscopy and/or retrograde pyelography showed a carcinoma of the renal pelvis in two patients and a carcinoma of the bladder in one patient. The patients with carcinoma of the renal pelvis died of cardiovascular complications within 2 years of nephroureterectomy. An autopsy was performed in one of these patients and there were no residual tumours or metastases. In the other patient autopsy was not performed, but urine cytology again suggested malignancy. The patient with a carcinoma of the bladder is still alive. She was treated with transurethral resection of the tumour and etoglucide instillations. We conclude that urine cytology is a good screening method for the early detection of transitional-cell carcinomas in dialysis patients with analgesic nephropathy.     

End-stage renal disease and renal replacement therapy in Kuwait--epidemiological proffle over the past 41/2 years

Data on end-stage renal disease (ESRD) patients in Kuwait werecollected retrospectively and prospectively starting in mid-1988.The study period covered 4 years from 1 January 1986 to 30 June1990. Epidemiological characteristics of ESRD patients and theirdisposal by dialysis and transplantation were analysed and comparedwith previous reports from Kuwait, neighbouring countries, Europe,and USA. A total of 647 patients received renal replacementtherapy (RRT) in Kuwait during the study period. This gave anincidence rate of 72 patients per year per million of population.The prevalence rate for patients on maintenance dialysis was80.6 per million population in mid-1988. Nearly one-fifth oftotal patients (19.6%) were older than 60 years of age and one-third(30.8%) were identified as ‘high risk’ category.As for Kuwaiti nationals alone on RRT 29.7% were above 60 yearsof age and 44.2% were high-risk patients. We have noticed asteady decline in the number of patients who accepted continuousambulatory peritonial dialysis (CAPD) for dialytic support. Chronic tubulointerstitial disease resulting from atrophic pyelonephritiswas the leading cause of ESRD amongst both Kuwaiti nationalsand expatriates. Though diabetic nephropathy was only the thirdlead ing cause of ESRD (14.7%) in the total population, it wasmore frequent (21.2%) among Kuwaitis. The gross mortality rateon dialysis was 14.7%. The major causes of death were relatedto cardiovascular diseases (60%) and sepsis (24.2%). Our analysisshowed that age of the patient at admission to dialysis contributedto overall mortality, but it was not an isolated risk factorwhereas diabetic nephropathy (relative risk 1.9) and associatedserious co-morbid illness/es (relative risk 30.3) were. Despitestrict precautionary measures in the dialysis units and earlyuse of erythropoietin, 68 new patients were detected to be HBsAgpositive, 85% of whom remained persistently antigenaemic formore than 6 months. At follow-up 9.8% (4/41) had died of liverfailure. The 50 months patient survival for patients who received unrelatedkidney transplantation (abroad) was lower than in those whoreceived live related kidneys in Kuwait. The most distressingobservation was, however, the very high patient loss associatedwith imported cadaver kidneys transplanted in Kuwait comparedto those who received cadaver kidneys harvested locally (65%versus 94.8% respectively at 16 months).     

Analgesic nephropathy: etiology, clinical syndrome, and clinicopathologic correlations in Australia.

Analgesic abuse is a major public health hazard in Australia, and analgesic nephropathy with consequent terminal renal failure is the underlying cause in 20% of the patients requiring dialysis and transplantation. Analgesics are invariably taken in the form of compounds and mixtures. In the aspirin-phenacetin-caffeine (APC) mixture, aspirin appears to be the major nephrotoxic agent and phenacetin appears to play a secondary and synergistic role. The renal disease associated with abuse of analgesics is characteristic and is part of a much wider clinical syndrome, the analgesic syndrome, which includes peptic ulcer disease (35%), anemia (60 to 90%), hypertension (15 to 70%), ischemic heart disease (35%), psychological and psychiatric manifestations, pigmentation, and possible gonadal- and pregnancy-related effects. The primary lesion in analgesic nephropathy is renal papillary necrosis (RPN), and this is a nephrotoxic effect common to all nonsteroid antiinflammatory agents. The most important factor in the management of patients with analgesic nephropathy is the cessation of analgesic abuse, and this leads to improvement and stabilization of renal function. A small proportion of patients will, however, deteriorate in relation to accelerated hypertension, persistent proteinuria, ischemic heart disease, and complications leading to nephrectomy. Patients with analgesic nephropathy are poor risk patients and have a poor prognosis, even after dialysis and transplantation.     

Atherosclerosis in patients with analgesic nephropathy treated with haemodialysis

SUMMARY: Accelerated atherosclerosis was reported to be associated with chronic analgesic consumption, but most studies were retrospective, and individual findings have almost never been controlled with regard to other atherosclerotic risk factors. Ten haemodialysis patients with analgesic nephropathy (group I) and 19 haemodialysis patients where renal failure was not caused by analgesic nephropathy (group II) were included in the study. All patients were female without diabetes. Using B-mode ultrasonography, we compared intima-media thickness (IMT) in the carotid arteries and plaque occurrence, and their thickness in group I with that in group II. the possible differences in atherosclerotic risk factors in both groups were also investigated. In group I, the average age was 60.2 years, and the average dialysis treatment was 55.7 months. In group II, the average age was 54.6 years, and the average duration of dialysis treatment was 50.4 months. We found no statistically significant difference in the age and duration of dialysis treatment between groups I and II. the IMT values of the carotid arteries (0.97 vs 0.78 mm; P = 0.027) were significantly higher in group I. More patients had plaques in group I (90 vs 57.9%), and the number of plaques ( P = 0.037) and their thickness ( P = 0.043) were significantly higher in this group. There was no statistically significant difference in the atherosclerotic risk factors between groups I and II. the results indicate that patients with analgesic nephropathy treated with haemodialysis showed advanced atherosclerosis compared with other haemodialysis patients, despite no difference being found in the atherosclerotic risk factors between these patients.     

Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: analysis of data from the United States,Europe, and Australia and New Zealand

Patients on maintenance dialysis have increased risk for cancer, especially in the kidney and urinary tract. In a retrospective cohort of 831,804 patients starting dialysis during 1980 to 1994 in the United States, Europe, or Australia and New Zealand, standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for kidney and bladder cancers. Risks for cancers of the kidney (SIR 3.6; CI 3.5 to 3.8) and bladder (SIR 1.5; CI 1.4 to 1.6) were increased, relatively more in younger than older patients and more in female patients (kidney: SIR 4.6, CI 4.3 to 4.9; bladder: SIR 2.7, CI 2.4 to 2.9) than male patients (kidney: SIR 3.2, CI 3.0 to 3.4; bladder: SIR 1.3, CI 1.2 to 1.3). SIR for kidney cancer were raised in all categories of primary renal disease, and for bladder cancer in all but diabetes and familial, hereditary diseases. Notably high SIR occurred in toxic nephropathies (chiefly analgesic nephropathy) and miscellaneous conditions (a category that includes Balkan nephropathy), the excess of kidney cancer in these conditions being urothelial in origin. SIR for kidney cancer rose significantly, and those for bladder cancer fell (not reaching significance) with time on dialysis. There was no association with type of dialysis. The pattern of increased risk for renal parenchymal cancer in dialysis patients is consistent with causation through acquired renal cystic disease and of urothelial cancers of the kidney and bladder with the carcinogenic effects of certain primary renal diseases.     

Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function

OBJECTIVE: Renovascular disease may lead to ischemia of the nephrons and to fibrosis, which is generally considered to be irreversible and progressive. We investigated the potential of revascularization to recover and stabilize renal function in patients with ischemic nephropathy. METHODS: In a retrospective analysis of all our 61 patients with ischemic nephropathy who underwent treatment with surgical revascularization, we determined the long-term course of renal function decline with an estimated glomerular filtration rate (EGFR; Cockcroft and Gault formula). With the assumption of normal renal function at age 25 years, the preoperative slope of EGFR and the postoperative slope of EGFR were determined from the EGFR before surgery, at the short-term follow-up examination (on average, 8 months after surgery), and at the long-term follow-up examination (on average, at 47 months after surgery). These declines in renal function were compared with EGFR values in age-matched and sex-matched samples from a large cross-sectional population study. RESULTS: The overall surgical mortality rate amounted to 13.1%. Five patients became dialysis dependent-two with preexisting end-stage renal disease and three at later follow-up examination-and two patients, who before surgery were dialysis dependent, could be withdrawn from dialysis treatment. Shortly after the operation, the mean EGFR level had increased from 28.3 to 43.1 mL/min/1.73 m2 ( P <. 01). The rate of decline in renal function had decreased from an estimated -2.57 mL/min/1.73 m2/year before surgery (weighted mean: interquartile range, -2.71 to -1.98) to -0.66 mL/min/1.73 m2/year (weighted mean: interquartile range, -2.00 to -0.18) in the short-term interval to the long-term interval, which was even slightly better than the slope of -0.84 mL/min/1.73 m 2/year in the age-matched and sex-matched control population. CONCLUSION: Surgical revascularization in selected patients with renovascular disease and ischemic nephropathy restores renal function and makes the average long-term rate of decline in renal function equal to that of the general population. This indicates that in most patients a "point-of-no-return" has not yet been passed even though their renal function is already markedly impaired before surgery. Therefore, in well-selected patients with ischemic nephropathy, considerable improvement of renal function can be realized.     

Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

BACKGROUND: Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. METHODS: To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. RESULTS: Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). CONCLUSION: Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.     

Strong association between IgA nephropathy and hepatitis B surface antigenemia in endemic areas

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 122 patients with primary IgA nephropathy. Hepatitis B surface (HBs) antigenemia was detected in 21 patients (17.2%) and this was significantly higher than the prevalence of HBsAg carrier in the general population (p less than 0.01). These patients had no clinical or laboratory findings to suggest acute or chronic liver diseases. Two glomerulopathic entities: mesangial proliferative glomerulonephritis with predominant mesangial IgA deposits and a mixed picture of membranous nephropathy with capillary IgG deposits and mesangial proliferative glomerulonephritis with mesangial IgA deposits, were observed in this group of patients. Glomerular deposits of HBsAg, hepatitis B core antigen (HBcAg), and both HBsAg and HBcAg were detected in three, five and four renal biopsy specimens respectively. Replication of hepatitis B virus (HBV) was suggested in two of the six renal biopsy specimens examined by HBV DNA gene probe. During the mean study period of 40 months (range 12-84), 19% of these patients with hepatitis B virus-associated IgA nephropathy developed progressive renal deterioration and one required maintenance dialysis therapy. Our study suggests that hepatitis B virus antigenemia may play a significant pathogenetic role in the development of IgA nephropathy in areas of high HBV endemicity and these HBV-associated IgA nephropathies can run an indolent but relentless slowly progressive clinical course.