Referral rate of chronic kidney disease patients to a nephrologist in the Region of Southern Denmark: results from KidDiCo.

Background: Data on the referral rate of chronic kidney disease (CKD) patients to specialists are sparse. Investigating referral rates and characterizing patients with kidney disease not followed by a nephrologist are relevant for future measures in order to optimize public health and guideline implementation. Methods: Data were extracted from the Kidney Disease Cohort of Southern Denmark (KidDiCo). Referral rates for all incident CKD patients below 60 mL/min/1.73 m² and referral rates according to the KDIGO guidelines based on glomerular filtration rates below 30 mL/min/1.73 m² were calculated. Information on contact with one of the nephrologist outpatient clinics in the Region of Southern Denmark was collected from the Danish National Patient Registry. The individual follow-up time for nephrology contact was 12 months. Additional data were accessed via the respective national databases. CKD patients on dialysis and kidney transplanted patients were excluded. Results: A total of 3% of patients with an eGFR <60 mL/min/1.73 m²-16% of patients with an eGFR <30 mL/min/1.73 m² and 35% of patients with an eGFR <15 mL/min/1.73 m² were in contact with a nephrologist in the outpatient settings. Younger age, male sex, diabetes, hypertension, higher education and proximity to a nephrology outpatient clinic increased the chance of nephrology follow-up. Conclusion: Only a small fraction of CKD patients are followed by a nephrologist. More studies should be performed in order to find out which patients will profit the most from renal referral and how to optimize the collaboration between nephrologists and general practitioners.

Hypertensive nephropathy is associated with an increased risk of myeloma, skin, and renal cancer.

Previous studies suggest an increased cancer risk in hypertension. Patients with hypertensive nephropathy have not been studied. A national registry study was performed to assess the presence and size of this association. Clinical data and cancer diagnoses for all patients with biopsy-proven hypertensive nephropathy between 1985 and 2015 in Denmark were extracted from four national registries and compared with age- and sex-adjusted national cancer rates. The risk of cancer was twice the background population. It was raised for renal cancer (odds ratio 10.4), myeloma (13.2), skin cancer (7.9), and other/unspecified (1.8). No increase in incidence was seen until 1 year before renal biopsy and then rose rapidly. It was again normal 5 years after biopsy. Hypertensive nephropathy is associated with an increased risk of myeloma, skin, renal, and other cancers. Screening of patients with hypertensive nephropathy, in the presence of reduced renal function or significant proteinuria, may be indicated.

Quantification of cancer risk in glomerulonephritis.

BACKGROUND: The association of increased cancer risk with glomerulonephritis (GN) is well known, but controversy exists concerning which types of GN are involved, and the size of the association. A national registry survey was performed to assess the size of this association, and the temporal relationship of cancer diagnosis to GN diagnosis. METHODS: All patients with biopsy-proven GN between 1985 and 2015 in Denmark were extracted from The Danish Renal Biopsy Registry and the National Pathology Data Bank. Incident cancer diagnoses between 10 years previous and 10 years subsequent to the GN diagnosis were extracted from the Danish Cancer Registry. Residence, birth and death data were obtained from the National Patient Register. Expected cancer incidence, classified according to cohort, age and sex were extracted from the Nordcan database. RESULTS: Nine hundred eleven cancers were diagnosed in 5594 patients. Thirty five percent were prevalent at renal biopsy. Prevalence at biopsy was 5.5% (expected 3.1%), but incidence was not increased < 1 year before biopsy. Increased cancer rates were seen for GN forms: minimal change, endocapillary, focal segmental glomerulosclerosis, mesangioproliferative, membranous, focal segmental, membranoproliferative, proliferative, ANCA-associated vasculitis, lupus nephritis and unclassified. Increased cancer rates were seen for lung, prostate, renal, non-Hodgkin lymphoma, myeloma, leukaemia and skin. The increased incidence was mainly limited to - 1 to 1 year after biopsy, but skin cancer showed an increased risk over time. Some diagnoses showed an increase 5-10 years after biopsy. Incidence was raised for patients with uraemia and nephrosis, but less for proteinuria or haematuria. Cancers in patients < 45 years were rare. The risk of developing cancer 0-3 years after biopsy for patients 45-64 years varied from 7.3% (minimal change) to 15.8% (unclassified GN); > 64 years from 11.8 (endocapillary GN) to 20.3% (unclassified). The diagnosis with the highest risk was membranoproliferative GN (8.6 & 19.6%). CONCLUSIONS: Cancer rates are increased for many cancer and most GN diagnoses. Cancer screening for patients < 45 years and for patients without nephrosis or uraemia may not be necessary. The findings suggest that screening programs for specific GN diagnoses can be extended to other GN forms.

Protein-bound solute removal during extended multipass versus standard hemodialysis.

BACKGROUND: Multipass hemodialysis (MPHD) is a recently described dialysis modality, involving the use of small volumes of dialysate which are repetitively recycled. Dialysis regimes of 8 hours for six days a week using this device result in an increased removal of small water soluble solutes and middle molecules compared to standard hemodialysis (SHD). Since protein-bound solutes (PBS) exert important pathophysiological effects, we investigated whether MPHD results in improved removal of PBS as well. METHODS: A cross-over study (Clinical Trial NCT01267760) was performed in nine stable HD patients. At midweek a single dialysis session was performed with either 4 hours SHD using a dialysate flow of 500 mL/min or 8 hours MPHD with a dialysate volume of 50% of estimated body water volume. Blood and dialysate samples were taken every hour to determine concentrations of p-cresylglucuronide (PCG), hippuric acid (HA), indole acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (PCS). Dialyser extraction ratio, reduction ratio, and solute removal were calculated for these solutes. RESULTS: Already at 60 min after dialysis start, the extraction ratio in the hemodialyser was a factor 1.4-4 lower with MPHD versus SHD, resulting in significantly smaller reduction ratios and lower solute removal within a single session. Even when extrapolating our findings to 3 times 4 h SHD and 6 times 8 h MPHD per week, the latter modality was at best similar in terms of total solute removal for most protein-bound solutes, and worse for the highly protein-bound solutes IS and PCS. When efficiency was calculated as solute removal/litre of dialysate used, MPHD was found superior to SHD. CONCLUSION: When high water consumption is a concern, a treatment regimen of 6 times/week 8 h MPHD might be an alternative for 3 times/week 4 h SHD, but at the expense of a lower total solute removal of highly protein-bound solutes.

Renal replacement therapy for rare diseases affecting the kidney: an analysis of the ERA-EDTA Registry.

BACKGROUND: In recent years, increased efforts have been undertaken to address the needs of patients with rare diseases by international initiatives and consortia devoted to rare disease research and management. However, information on the overall prevalence of rare diseases within the end-stage renal disease (ESRD) population is limited. The aims of this study were (i) to identify those rare diseases within the ERA-EDTA Registry for which renal replacement therapy (RRT) is being provided and (ii) to determine the prevalence and incidence of RRT for ESRD due to rare diseases, both overall and separately for children and adults. METHODS: The Orphanet classification of rare disease was searched for rare diseases potentially causing ESRD, and these diagnosis codes were mapped to the corresponding ERA-EDTA primary renal disease codes. Thirty-one diagnoses were defined as rare diseases causing ESRD. RESULTS: From 1 January 2007 to 31 December 2011, 7194 patients started RRT for a rare disease (10.6% children). While some diseases were exclusively found in adults (e.g. Fabry disease), primary oxalosis, cystinosis, congenital anomalies of the kidney and urinary tract (CAKUT) and medullary cystic kidney disease affected young patients in up to 46%. On 31 December 2011, 20 595 patients (12.4% of the total RRT population) were on RRT for ESRD caused by a rare disease. The point prevalence was 32.5 per million age-related population in children and 152.0 in adults. Only 5.8% of these patients were younger than 20 years; however, 57.7% of all children on RRT had a rare disease, compared with only 11.9% in adults. CAKUT and focal segmental glomerulosclerosis were the most prevalent rare disease entities among patients on RRT. CONCLUSIONS: More than half of all children and one of nine adults on RRT in the ERA-EDTA Registry suffer from kidney failure due to a rare disease, potentially with a large number of additional undiagnosed or miscoded cases. Comprehensive diagnostic assessment and the application of accurate disease classification systems are essential for improving the identification and management of patients with rare kidney diseases.

Mesangioproliferative glomerulonephritis: a 30-year prognosis study.

BACKGROUND: Diffuse mesangioproliferative glomerulonephritis (MesP) is the most commonly diagnosed type of glomerulonephritis (GN) in Denmark, with an incidence of 10.8 million per year. In the present study, the 30-year renal survival was estimated. METHODS: A retrospective cohort investigation of 140 patients with biopsy-proven MesP was performed between the period 1967-2006. Factors influencing renal survival were investigated using Cox regression analysis. RESULTS: Renal survival at 5, 10, 20 and 30 years was 87, 78, 59 and 50%, respectively. Female survival after 30 years was significantly better than male survival (70 vs. 40%, p = 0.049). Multivariate analysis, adjusted for age, estimated glomerular filtration rate (GFR) and nephrotic syndrome (NS) was performed for each sex individually. An increase in GFR was associated with a hazard risk (HR) of 0.98 (p = 0.02) in women and 0.99 (p = 0.006) in men. Older age was associated with a HR of 1.04 (p = 0.02) in women and 1.03 (p = 0.004) in men. NS had a poorer prognosis in men (HR 2.53, p = 0.01), but not in women (HR 0.54, p = 0.38). CONCLUSION: Increasing age and decreasing GFR were adversely associated with renal death. Renal prognosis was better for women after 30 years, and NS resulted in a poorer prognosis in men. This suggests that disease course and prognosis are different between men and women.

Indexing glomerular filtration rate to body surface area: clinical consequences.

BACKGROUND: Kidney function is mostly expressed in terms of glomerular filtration rate (GFR). A common feature is the expression as ml/min per 1.73 m(2) , which represents the adjustment of the individual kidney function to a standard body surface area (BSA) to allow comparison between individuals. We investigated the impact of indexing GFR to BSA in cancer patients, as this BSA indexation might affect the reported individual kidney function. METHODS: Cross-sectional study of 895 adults who had their kidney function measured with (51) chrome ethylene diamine tetraacetic acid. Mean values of BSA-indexed GFR vs. mean absolute GFR were analyzed with a t-test for paired data. Bland-Altman plot was used to analyze agreement between the indexed and absolute GFR values. RESULTS AND CONCLUSION: BSA-GFR in patients with a BSA <1.60 m(2) overestimated GFR with a bias of 10.08 ml/min (11.46%) and underestimated GFR in those with a BSA >2 m(2) with a bias up to -20.76 ml/min (-23.59%). BSA is not a good normalization index (NI) in patients with extreme body sizes. Therefore, until a better NI is found, we recommend clinicians to use the absolute GFR to calculate individual drug chemotherapy dosage as well as express individual kidney function.

Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract.

BACKGROUND AND OBJECTIVES: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of ESRD in children, but the proportion of patients with individual CAKUT entities progressing to ESRD during adulthood and their long-term clinical outcomes are unknown. This study assessed the age at onset of renal replacement therapy (RRT) and patient and renal graft survival in patients with CAKUT across the entire age range. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with CAKUT were compared with age-matched patients who were undergoing RRT for other renal disorders on the basis of data from the European Renal Association-European Dialysis and Transplant Association Registry. Competing risk and Cox regression analyses were conducted. RESULTS: Of 212,930 patients commencing RRT from 1990 to 2009, 4765 (2.2%) had renal diagnoses consistent with CAKUT. The proportion of incident RRT patients with CAKUT decreased from infancy to childhood and then increased until age 15-19 years, followed by a gradual decline throughout adulthood. Median age at RRT start was 31 years in the CAKUT cohort and 61 years in the non-CAKUT cohort (P<0.001). RRT was started earlier (median, 16 years) in patients with isolated renal dysplasia than in those with renal hypoplasia and associated urinary tract disorders (median, 29.5-39.5 years). Patients with CAKUT survived longer than age- and sex-matched non-CAKUT controls because of lower cardiovascular mortality (10-year survival rate, 76.4% versus 70.7%; P<0.001). CONCLUSIONS: CAKUT leads to ESRD more often at adult than pediatric age. Treatment outcomes differ from those of acquired kidney diseases and vary within CAKUT subcategories.