The relative prognosis of nodular and diffuse diabetic nephropathy.

MATERIAL AND METHODS: One hundred and forty-four diabetic patients with biopsy-proven diffuse diabetic glomerulosclerosis (DIF), 134 patients with nodular diabetic nephropathy (NOD) and 152 diabetic patients with nondiabetic-related morphology (104 chronic nephropathy, 48 primary GN) were followed for up to 12 years to determine the clinical prognosis. RESULTS: Comparing the NOD patients with the DIF patients, there were more females (41% vs 26%, p < 0.05) and they were more often uremic at biopsy (24% vs 12%, p < 0.01), but the age was similar (53.3 years vs 50.1 years, NS). There was no difference in diabetes type I and II incidence. Compared with the general population, the odds ratio (OR) for death was 7.2 (confidence interval 5.5-9.5) for DIF and 10.8 (8.5-13.7) for NOD. The OR for combined renal or patient death was: DIF 15.2 (11.7-19.7); NOD 24.6 (19.4-31.0). After correction for age, sex, and pre-existing uremia, NOD had a 1.70 (p < 0.01) times increased risk of death compared with DIF, and a 2.42 (p < 0.01) times increased risk of renal failure. The life expectancy for NOD was 4.0 years, and average time to dialysis was 2.1 years. NOD prognosis was similar to other chronic nephropathy. The incidence of all atherosclerotic complications except AMI was twice as high in NOD than DIF. Diabetes type had no influence on prognosis. The estimated incidence of diabetic nephropathy was 56/mio/year. CONCLUSION: Nodular diabetic nephropathy has a poorer prognosis than diffuse due to a higher rate of atherosclerotic and uremic complications.

Cancer risk in patients on dialysis and after renal transplantation.

The increased risk of cancer in patients who have had kidney transplants has mainly been attributed to immunosuppressive therapy; however, the prior period of uraemia and dialysis has also been postulated as a cofactor. We analysed cancer risk retrospectively in a cohort of 4178 patients undergoing renal replacement therapy, of whom 3592 were treated with dialysis alone and 1821 later had transplants. We found that excess cancer risk in such patients occurred after transplantation and not during dialysis.

[Living-donor kidney transplantation]. / Nyretransplantation med levende donor.

In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associated with only few complications. The long-term outcome for kidney donors is good without increase in mortality or risk for development of hypertension and renal failure; proteinuria may be seen. Living kidney transplantation is the optimal treatment of end-stage renal disease with better graft survival than in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients.

Kidney transplantation activity and outcome in Denmark 1990-1999.

1. During the period 1990-1999, 1,715 renal transplants were performed in Denmark, corresponding to 31.8 per million population per year. Seventy-five per cent were cadaver donor transplants; in 25%, a living donor kidney was used. 2. Living donors of 437 kidneys were mainly parents (54%) and siblings (36%). In 20 transplants, a kidney from a living-unrelated donor was used. 3. The overall actuarial patient survival rates at one and 5 years were 91.0% and 78.2%, respectively. The major causes of recipient death were cardiovascular disease and infection. 4. The overall actuarial graft survival rates at one and 5 years were 81.4% and 62.0%, respectively. The major single causes of graft loss were rejection (41%) and recipient death (32%). Graft survival has improved during the decade.

The epidemiology and prognosis of glomerulonephritis in Denmark 1985-1997.

BACKGROUND: The existence of a national renal biopsy register and a national terminal uraemia status register in Denmark provides an opportunity to study the prognosis of glomerulonephritis (GN), and factors influencing prognosis. METHODS: Multivariate analysis of 2380 renal biopsies with GN performed between 1985 and 1997 was done to determine the influence of clinical and histological factors on prognosis. RESULTS: The incidence of GN (39/mo/year) and individual diagnoses did not change during the period. After 10 years, 32%, were dead, 13% terminally uraemic, 5%, uraemic and 50% well. Older age increased mortality, but not the incidence of renal failure after the first year. Male sex increased both mortality and incidence of renal failure (34 vs 24% at 10 years, P < 0.001). The diagnoses could be divided into three prognostic groups compared with the general population: a good prognostic group (minimal change GN and membranous GN ), with a relative mortality of three and a combined renal and patient mortality of four; a poor prognostic group [crescentic GN, HUS/TTP, chronic GN] with relative mortalities of 8-19 and 13-33, respectively; and the remainder with mortalities of 4-7 and 6-12. The presence of multiple glomerular pathology, chronic GN, nephrosclerosis and chronic interstitial nephropathy worsened the prognosis, while the presence of immune deposits only worsened the prognosis of focal segmental glomerulopathy. Mortality was related to uraemia and co-morbidity at biopsy, and to the incidence of renal failure. Renal failure was correlated to uraemia and hypertension at biopsy but not to nephrotic syndrome or atherosclerosis. All vascular complications were increased and were positively related to hypertension and negatively correlated to the incidence of uraemia. Crescentric glomerulonephritis combined with anti-GBM disease had a worse prognosis than Wegener's granulomatosis, with microscopic polyangiitis and pauci-immune disease occupying an intermediate position. The prognosis of mesangioproliferative GN was unaffected by the presence of IgA nephropathy and systemic lupus erythematosus.

Perioperative Doppler ultrasonography: renal detection of renal graft perfusion.

Irreversible damage of renal transplants may be prevented if insufficient graft perfusion can be detected perioperatively. Colour and spectral Doppler ultrasonography were performed in 30 consecutive renal transplants. The perfusion of the graft and the Resistive Index (RI) were evaluated perioperatively (perioperatively and less than 15 min postoperatively) and 24 h after the operation in all patients. In four cases (13.3%) RI > 0.9 was detected and immediate surgical correction of the cause led to a normalization (RI < 0.8) in all four cases. A RI < 0.9 required no intervention in 26 cases (86.7%). All renal grafts in this series were functioning 1 month postoperatively. In a comparative group, 30 consecutive transplants carried out at our institution without perioperative Doppler ultrasonography evaluation, a loss of four renal grafts perioperatively was recorded retrospectively. We conclude that perioperative ultrasonography Doppler evaluation may provide an easy applicable and reliable method for early detection of insufficient renal graft perfusion, allowing surgical correction before irreversible damage of the graft occurs. RI > 0.9 is pathological. A continuation of the study is required to clarify the long-term value of perioperative Doppler ultrasonography graft monitoring.

[Predicting the number of patients on dialysis and renal transplant recipients in Denmark]. / Prognose for antallet af dialyse- oq transplantationspatienter i Danmark.

A Markov model was applied in three ways: 1) a deterministic model with fixed rates, 2) a stochastic model using simulated varying rates and 3) a deterministic model with increasing rates. With present rates an increase in the prevalence of renal transplant recipients < 60 years (from 1003 in 1995 to about 1465 in 2006) and the prevalence of haemodialysis patients less than or equal to 60 years (from 456 in 1995 to about 903 in 2006) was predicted. The prevalence in other treatment modalities would change less. The overall prevalence proportion would increase from 539 patients/mio. inhabitants in 1995 to about 777/mio. in 2006. Observed and expected numbers with the stochastic model in 1996 were: haemodialysis: 1053 (1074 +/- 41, 2p = 0.61), peritoneal dialysis: 456 (480 +/- 22, 2p = 0.28) and renal transplant recipients: 1232 (1266 +/- 14, 2p = 0.015). The deterministic model with increasing rates predicted an overall prevalence of 1162 patients/mio. in 2006.

Risk factors in haemodialysis patients: evaluation of commonly measured variables on death rate.

This study evaluates risk factors among commonly measured laboratory values and clinical findings in haemodialysis patients, followed by attempts to identify optimal treatment strategies. Average plasma concentrations of albumin, protein, CO2, urea and creatinine, and average values of systolic and diastolic blood pressure, together with information on gender, age and renal diagnosis, were related to survival rate in 210 sequences of haemodialysis treatment during a period of 94 months. The average treatment time was 12.6 months (range 1-94). The material was analysed with stepwise regression analysis using the Cox proportional hazard model (BMDP 2L), and actuarial life table analysis was performed to illustrate the magnitude of influence of the independent variables on patient survival (BMDP IL). Patient survival was negatively correlated with age and positively correlated with average plasma concentrations of albumin. Surprisingly, patient survival was negatively correlated with plasma CO2. Patient survival was significantly lower in diabetics.

Predicting future trends in the number of patients on renal replacement therapy in Denmark.

OBJECTIVES: To predict the future prevalence of patients on renal replacement therapy due to chronic renal failure in Denmark. SUBJECTS AND METHODS: Four thousand and nine terminal uraemic patients (median age 50.0 years, 15.2% diabetic) were treated in Denmark with renal replacement therapy in the period 1 January 1991 to 31 December 1995. Incidence rates and rates of transition between the treatment modalities (haemodialysis, peritoneal dialysis, and renal transplantation) were calculated. The prediction was made using a Markov model in three ways: (1) using the average rates (deterministic model), (2) using rates simulated with pseudorandom numbers based on the average rates (stochastic model), and (3) using increasing incidence rates in a deterministic model. RESULTS: Using present rates both model types predicted a significant increase in the prevalence of renal transplant recipients < 60 years (from 1003 in 1995 to about 1465 in 2006) and the prevalence of haemodialysis patients > or = 60 years (from 456 in 1995 to about 903 in 2006) while the prevalence of other treatment modalities would change less dramatically. The overall prevalence proportion would increase from 539 patients per million population (p.m.p.) in 1995 to about 777 p.m.p. in 2006. The stochastic model clearly demonstrated the uncertainties linked to the prognosis in contrast to the deterministic model. The deterministic model with increasing rates predicted a prevalence proportion of 1162 p.m.p. in 2006. CONCLUSION: Even with present rates the prevalence of haemodialysis patients in Denmark will continue to increase. Mathematical models offers a good tool to study future trends and to plan future capacity.

Consistent absorption of cyclosporine from a microemulsion formulation assessed in stable renal transplant recipients over a one-year study period.

To evaluate the pharmacokinetic properties of the new microemulsion formulation of cyclosporine (Sandimmun Neoral), a double-blind, prospective study in stable renal transplant recipients was performed. The patients were randomized on a 4:1 basis either to receive Sandimmun Neoral (n = 45) or continue on regular Sandimmun (n = 12). Before randomization, a steady-state pharmacokinetic profile study was performed in all patients while they were still on regular Sandimmun. Pharmacokinetic assessments were then performed after 8 and 12 weeks and after 1 year. A milligram-to-milligram dose conversion was shown to be adequate to maintain the patients within a predefined target therapeutic window. Changes in pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent with an increased rate and extent of cyclosporine absorption from the Neoral formulation. This was reflected by a shorter time to reach peak concentration and also by a mean increase in peak concentration by 67%, and an overall mean increase in drug exposure (area under the curve) by 34%. These findings were also confirmed 1 year after conversion. Furthermore, significantly reduced intraindividual variability in pharmacokinetic parameters was found, as well as improvements in the correlation between trough concentrations and area under the curve after conversion to Sandimmun Neoral. In conclusion, our results indicate an improved and consistent absorption of cyclosporine from the Neoral formulation, which should make clinical management easier and safer.

[Prognosis for patients admitted to intensive care units with acute renal failure requiring dialysis]. / Prognosen for patienter indlagt på intensiv afdeling med dialysekraevende akut nyresvigt.

The mortality of critically ill patients who develop acute renal failure (ARF) is persistingly high. We reviewed all patients who developed ARF that required dialysis in a single intensive care unit (n = 167) during the period 1977 to 1989, in order to identify variables with possible influence on outcome. Overall mortality within hospital was 75%. Age above 60 (p < 0.02), requirement for mechanical ventilation (p < 0.0005), requirement for inotropic drugs (p < 0.0005) and increased levels of P-bilirubin (p < 0.005) had negative impacts on survival. Mortality increased significantly from 63% in the early period (1977-1985) to 84% in the late period (1986-1989) (p < 0.001), a rise that could not be explained by a single variable. The patients in the later period were, though, characterized by a higher morbidity with a higher frequency of additional organ failure.

No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

Transperitoneal transport of creatinine. A comparison of kinetic models.

Six kinetic models of transperitoneal creatinine transport were formulated and validated on the basis of experimental results obtained from 23 non-diabetic patients undergoing peritoneal dialysis. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. The validation procedure included an assessment of theoretical (a priori) and practical (a posteriori) identifiability, goodness of fit, residual error analysis and plausibility of parameter estimates. The results of the validation procedure demonstrate that the model including all three forms of transport is superior to other models. We conclude that the best model of transperitoneal creatinine transport includes diffusion, non-lymphatic convective transport and lymphatic convective transport.

[Renal insufficiency in myelomatosis. Causes and treatment]. / Nyreinsufficiens ved myelomatose. Arsager og behandling.

Renal failure is a frequent complication in multiple myeloma and it is present in about 50% of patients with newly-diagnosed multiple myeloma. Renal failure at the time of diagnosis has earlier been associated with a bad prognosis, but a better prognostic factor is the response to chemotherapy. In general, it is important to distinguish between 1) renal insufficiency at the time of diagnosis, 2) acute renal insufficiency and 3) chronic renal insufficiency developing during the course of the disease. The patients in the first two groups are treated with intensive therapy which is long-lasting (median four to six weeks). The improved function of the kidney is correlated to an improved survival. Patients developing chronic renal insufficiency late in the course of the disease should receive palliative therapy. The most important factors that provoke acute renal insufficiency are dehydration, hypercalcaemia and/or infection, but renal insufficiency is also provoked by the use of nephrotoxic drugs, hyperuricaemia and/or hyperviscosity. Chronic renal insufficiency is provoked by deposits of light chains, infiltration by plasma cells or deposits of amyloid. The treatment consists of elimination of the provoking factors and start of chemotherapy.

Changes in blood and plasma volume during treatment with recombinant human erythropoietin.

18 chronic dialysis patients with renal anemia were examined before and after three months of regular treatment with recombinant human erythropoietin (EPO). All patients responded with an increase in hemoglobin concentration (cHb). The target cHb of 7.0 mmol/L was subsequently maintained by one subcutaneous injection a week, obviating the need of blood transfusions. The amount of circulating hemoglobin and the volume of erythrocytes increased, but the plasma volume simultaneously decreased, maintaining a constant blood volume. Although some of the individual blood volumes varied, the relation between circulating hemoglobin and the hemoglobin concentration still existed. We conclude that the hemoglobin concentration gives an accurate measure of the degree of anemia, and measurement of circulating hemoglobin is unnecessary during routine treatment of dialysis patients with EPO.