Long-term Renal Function Impairment Research Articles

Oncological and functional outcome of robotic-assisted radical cystectomy with total intracorporeal stentless J-pouch neobladder reconstruction.

Robotic-assisted radical cystectomy (RARC) with neobladder reconstruction has gained popularity in recent years. We conducted a retrospective study of 17 consecutive patients who underwent RARC with totally intracorporeal J-pouch neobladder reconstruction without ureteral stent by a single experienced surgeon to evaluate perioperative, oncological and functional outcomes. The median follow-up duration was 32.8months (range: 17.4-59.0months), and the 2-year disease-free survival rate was 88.2%. Five out of 12 patients were totally continent, and none required more than one pad per day. The overall complication rate was 41.2%, and hydronephrosis was the most common adverse event. The renal function remained stable, and no long-term renal function impairment was detected. Our study suggests that RARC with totally intracorporeal J-pouch neobladder reconstruction without ureteral stent is a safe and feasible option for the treatment of muscle-invasive bladder cancer, with good oncological and functional outcomes.

A new machine-learning model to predict long-term renal function impairment after minimally invasive partial nephrectomy: the Fundació Puigvert predictive model.

To provide a new model to predict long-term renal function impairment after partial nephrectomy (PN). Data of consecutive patients who underwent minimally invasive PN from 2005 to 2022 were analyzed. A minimum of 12 months of follow-up was required. We relied on a machine-learning algorithm, namely classification and regression tree (CART), to identify the predictors and associated clusters of chronic kidney disease (CKD) stage migration during follow-up. 568 patients underwent minimally invasive PN at our center. A total of 381 patients met our inclusion criteria. The median follow-up was 69 (IQR 38-99) months. A total of 103 (27%) patients experienced CKD stage migration at last follow-up. Progression of CKD stage after surgery, ACCI and baseline CKD stage were selected as the most informative risk factors to predict CKD progression, leading to the creation of four clusters. The progression of CKD stage rates for cluster #1 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI 1-4), #2 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI ≥ 5), #3 (no progression of CKD stage after surgery and baseline CKD stage 3-4-5) and #4 (progression of CKD stage after surgery) were 6.9%, 28.2%, 37.1%, and 69.6%, respectively. The c-index of the model was 0.75. We developed a new model to predict long-term renal function impairment after PN where the perioperative loss of renal function plays a pivotal role to predict lack of functional recovery. This model could help identify patients in whom functional follow-up should be intensified to minimize possible worsening factors of renal function.

PE077 - Prediction of long-term renal function impairment after minimally invasive partial nephrectomy through a new CART-based model.

PE077 - Prediction of long-term renal function impairment after minimally invasive partial nephrectomy through a new CART-based model.

Radiation therapy for nonmetastatic medically inoperable upper-tract urothelial carcinoma.

BackgroundThe standard management for upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). However, some patients cannot undergo this procedure for several reasons, such as unresectable disease, old age, and multiple comorbidities. Our study explored the potential safety and effectiveness of radiotherapy as a curative treatment for UTUC patients unfit for surgery.MethodsThe data of patients treated with radiotherapy between December 2017 and November 2019 were retrospectively reviewed. For the literature review, computerized PubMed Medline, Index Medicus, and Web of Science databases and reference lists from the identified publications of interest were used. And “upper-tract urothelial carcinoma” and “radiotherapy” were used as key words in the search.ResultsWe describe 8 patients with UTUC who were treated with radiotherapy. The median follow-up time was 13.5 months (range, 8.6–30.9 months). Local tumor control was achieved in all patients. However, distant metastases were observed in 2 patients with T3-4/N+ status. One patient had T4 status and the other had N2+ status. The patients died of tumor progression at 15.0 and 17.7 months. In addition, the other 6 patients who were still alive had relatively early-stage tumors without nodal involvement. Regarding acute toxicity, according to the CTCAE v5.0, mild side effects were noted, including grade 1 nausea and diarrhea. Four patients developed mild anemia, generally of grade 1–2. One patient experienced grade 3 anemia, but it was manageable and improved with symptomatic support. In addition, no grade 4 acute or late toxicities were observed. No significant long-term impairment of renal function occurred.ConclusionsFor patients with nonmetastatic UTUC who are not suitable for surgery, radiotherapy is a safe treatment and can achieve good local tumor control.

Radionuclide techniques for the detection of vesicoureteral reflux and their clinical significance.

We discuss and try to evaluate the detection of vesicoureteral reflux (VUR) by radionuclide techniques and especially direct radionuclide cystography (DRC). Direct radionuclide cystography is applied for more than half a century mainly in children. Vesicoureteral reflux has a complex pathology not yet completely understood and is often related to urinary tract infection (UTI) and renal parenchyma scarring that can lead to long-term renal function impairment. Since there is no consensus on the optimal imaging algorithm after the first febrile urinary tract infection, many imaging strategies have been proposed for VUR detection in the last decade, including or not DRC. Views opposing or accepting its use are also presented.

Comparison of a Significant Decline in the Glomerular Filtration Rate between Ileal Conduit and Ileal Neobladder Urinary Diversions after Radical Cystectomy: A Propensity Score-Matched Analysis

Urinary diversion after radical cystectomy is associated with a risk of renal function impairment. A significant decline in the glomerular filtration rate (GFR) (i.e., a ≥30% decline in baseline GFR after 12 months) is associated with long-term renal function impairment. We compared the significant GFR decline between ileal conduit and ileal neobladder urinary diversions 12 months after radical cystectomy. We retrospectively included radical cystectomy patients. Propensity score-matched analysis was performed. The primary outcome was the incidence of a significant GFR decline in ileal conduit urinary diversion (ileal conduit group) and ileal neobladder urinary diversion (ileal neobladder group) 12 months after radical cystectomy. The secondary outcomes were the change of GFR and the incidence of end-stage renal disease (ESRD) in the two groups. After propensity score matching, the ileal conduit and neobladder groups had 117 patients each. The incidence of a significant GFR decline was not significantly different between ileal conduit and ileal neobladder groups (12.0% vs. 13.7%, p = 0.845). The change of GFR and ESRD incidence were not significantly different between the two groups (−8.4% vs. −9.7%, p = 0.480; 4.3% vs. 5.1%, p > 0.999, respectively). These results can provide important information on appropriate selection of the urinary diversion type in radical cystectomy.

Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis.

In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment. Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3-26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies. Despite a moderate correlation between urinary protein/creatinine ratios (UPCR) and AI scores at repeat biopsy (r = 0.48; P = 0.001), 10 patients (23.8%) with UPCR < 1.0 g/g still had a high degree of histological activity (AI > 3). High AI scores (continuous) in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (n = 11) following the repeat biopsy [hazard ratio (HR) = 1.2, 95% CI: 1.1, 1.3; P = 0.007], independently of proteinuria levels. High CI scores (continuous) in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR = 1.8, 95% CI: 1.1, 2.9; P = 0.016) through a median (IQR) follow-up time of 131.5 (73.8-178.2) months, being also the case for acute tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in repeat but not baseline biopsies. Our results highlight the usefulness of per-protocol repeat biopsies, herein performed after a median time of 24 months from baseline, as an integral part of the treatment evaluation, also in patients showing adequate clinical response.

Role of Clinical and Surgical Factors for the Prediction of Immediate, Early and Late Functional Results, and its Relationship with Cardiovascular Outcome after Partial Nephrectomy: Results from the Prospective Multicenter RECORd 1 Project

We sought to determine the predictors of short-term and long-term renal function impairment after partial nephrectomy. Clinical data on 769 consecutive patients who underwent partial nephrectomy were prospectively recorded at a total of 19 urological Italian centers from 2009 to 2012 in the RECORd 1 (Italian Registry of Conservative Renal Surgery) Project. We extracted clinical data on 708 of these patients who were alive, free of recurrent disease and with a minimum 2-year functional followup. Of the patients 47.3% underwent open, 36.6% underwent laparoscopic and 16.1% underwent robot-assisted partial nephrectomy. The median baseline estimated glomerular filtration rate was 84.5 ml/minute/1.73 m2 (IQR 69.9-99.1). Immediate (day 3 postoperatively), early (month 1) and late (month 24) renal function impairment greater than 25% from baseline was identified in 25.3%, 21.6% and 14.8% of cases, respectively. Female gender and the baseline estimated glomerular filtration rate were independent predictors of immediate, early and late renal function impairment. Age at diagnosis was an independent predictor of immediate and late impairment. Uncontrolled diabetes was an independent predictor of late impairment only. Open and laparoscopic approaches, and pedicle clamping were independent predictors of immediate and early renal function impairment. Overall 58 of 529 patients (11%) experienced postoperative cardiovascular events. Body mass index and late renal function impairment were independent predictors of those events. Surgically modifiable factors were significantly associated with worse immediate and early functional outcomes after partial nephrectomy while clinically unmodifiable factors affected renal function during the entire followup. Late renal function impairment is an independent predictor of postoperative cardiovascular events.

Long-term Renal Function After Urinary Diversion by Ileal Conduit or Orthotopic Ileal Bladder Substitution

BackgroundData on long-term renal function are scarce for ileal conduit diversion (ICD) and even rarer for orthotopic ileal bladder substitution (BS). ObjectiveExplore the changes in renal function of patients who lived ≥10 yr with an ICD or BS and determine the risk factors contributing to renal function deterioration. Design, setting, and participantsFifty consecutive ICD patients and 111 consecutive BS patients who lived ≥10 yr after undergoing surgery between January 1985 and December 2000 were retrospectively analyzed. MeasurementsThe glomerular filtration rate (GFR) was calculated with the Modification of Diet in Renal Disease (MDRD) equation before and 10 yr after surgery. Decreased renal function was defined as a decrease in GFR >10ml/min per 1.73 m2 in 10 yr. Results and limitationsMedian GFR values in patients with ICD or BS decreased from 65.5 (range: 23–90) to 57 (range: 7–100) ml/min per 1.73 m2 and from 68 (range: 33–106) to 66 (range: 16–100) ml/min per 1.73 m2, respectively. Eighteen ICD patients (36%) and 23 BS patients (21%) had deteriorating renal function. Seven of 12 ICD patients with obstruction (ureteroileal stricture, stomal stenosis/parastomal hernia) (58%) had renal function deterioration, as did 17 of 46 BS patients with obstruction (ureteroileal/nipple stricture and/or bladder outlet obstruction) (37%). Logistic regression analysis confirmed that obstruction was the leading, and an independent, risk factor for renal function deterioration for both ICD patients (p=0.045) and BS patients (p=0.002). Patients with diabetes or hypertension were significantly more likely to have deterioration of renal function if they had ICD (p=0.002 and p=0.05, respectively). The limitation of the study is its retrospective nature and its composition that included many patients who did not survive 10 yr. ConclusionsUrinary tract obstruction was the leading cause of long-term renal function impairment, regardless of whether the patient had ICD or BS. ICD patients with predisposing risk factors, such as diabetes or hypertension, were at increased risk for impaired renal function.

Editorial Comment

No AccessJournal of UrologyAdult Urology1 Jan 2009Editorial Comment Paul Russo Paul RussoPaul Russo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.09.138AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, 181(1), pp. 53–54 References 1 : Surgical renal ischemia: a contemporary overview. J Urol2008; 180: 19. Link, Google Scholar 2 : Temporary renal ischemia during nephron-sparing surgery is associated with short-term but not long-term impairment of renal function. J Urol2006; 176: 1339. Link, Google Scholar 3 : Long-term changes in creatinine clearance after laparoscopic renal surgery. J Am Coll Surg2008; 206: 511. Google Scholar Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York© 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 181Issue 1January 2009Page: 53-54 Advertisement Copyright & Permissions© 2009 by American Urological AssociationMetricsAuthor Information Paul Russo More articles by this author Expand All Advertisement PDF downloadLoading ...

Chronic kidney disease in older people: diagnosis, pathogenesis and management

Chronic kidney disease (CKD) refers to long-term impairment of renal function. It is predominantly a disease of older people and the true extent of this has only recently been recognized. CKD has a number of implications including increased cardiovascular risk, secondary complications such as renal anaemia and bone disease and a small but significant risk of progression to established renal failure (ERF). It is associated with significant morbidity, mortality and healthcare costs and, against the background of an ageing population and the rising prevalence of type 2 diabetes, represents a growing public health problem. Evidence that specific interventions can reduce the cardiovascular risk associated with CKD and the risk of progressive CKD, as well as improving quality of life, has highlighted the importance of early detection of this disease.

Candesartan prevents long-term impairment of renal function in response to neonatal partial unilateral ureteral obstruction

Angiotensin II (ANG II) plays an important role in the development of obstructive nephropathy. Here, we examined the effects of the ANG II receptor type 1 (AT1R) blockade using candesartan on long-term renal molecular and functional changes in response to partial unilateral ureteral obstruction (PUUO). Newborn rats were subjected to severe PUUO or sham operation (Sham) within the first 48 h of life. Candesartan was provided in the drinking water (10 mg.kg(-1).day(-1)) from day 21 of life until 10 wk of age. Renal blood flow (RBF) was evaluated by MRI, glomerular filtration rate (GFR) was measured using the renal clearance of (51)Cr-EDTA, and the renal expression of Na-K-ATPase and the collecting duct water channel aquaporin-2 (AQP2) was examined by immunoblotting and immunocytochemistry. At 10 wk of age, PUUO significantly reduced RBF (0.8 +/- 0.1 vs. 1.6 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and GFR (37 +/- 16 vs. 448 +/- 111 microl.min(-1).100 g body wt(-1); P < 0.05) compared with Sham. Candesartan prevented the RBF reduction (PUUO+CAN: 1.6 +/- 0.2 vs. PUUO: 0.8 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and attenuated the GFR reduction (PUUO+CAN: 265 +/- 68 vs. PUUO: 37 +/- 16 microl.min(-1).100 g body wt(-1); P < 0.05). PUUO was also associated with a significant downregulation in the expression of Na-K-ATPase (75 +/- 12 vs. 100 +/- 5%, P < 0.05) and AQP2 (52 +/- 15 vs. 100 +/- 4%, P < 0.05), which were also prevented by candesartan (Na-K-ATPase: 103 +/- 8 vs. 100 +/- 5% and AQP2: 74 +/- 13 vs. 100 +/- 4%). These findings were confirmed by immunocytochemistry. Consistent with this, candesartan treatment partly prevented the reduction in solute free water reabsorption and attenuated fractional sodium excretion in rats with PUUO. In conclusion, candesartan prevents or attenuates the reduction in RBF, GFR and dysregulation of AQP2 and Na-K-ATPase in response to congenital PUUO in rats, suggesting that AT1R blockade may protect the neonatally obstructed kidney against development of obstructive nephropathy.

Long-term outcome of kidney function after twin–twin transfusion syndrome treated by intrauterine laser coagulation

Twin-twin transfusion syndrome (TTTS) is caused by unbalanced shunting of blood between monochorionic twins. It is well known that chronic hypotension and hypovolemia may cause renal insufficiency in the donor twin. The long-term outcome of kidney function after TTTS has not previously been delineated in the literature, however. The aim of this study was to evaluate the long-term outcome of kidney function in children after intrauterine laser treatment for severe TTTS. Eighteen surviving twin pairs after intrauterine laser treatment for TTTS were involved in the study. Their gestational age at birth was 29-39 weeks, their median birth weight was 2050 g, and their median age at evaluation was 3 years 1 month, range 1 year 9 months to 4 years 5 months. Serum creatinine, cystatin C, and beta 2-microglobulin, sodium, potassium, and phosphate excretion, and urine albumin and alpha-1-microglobulin were measured. Creatinine clearance was calculated by use of the Schwartz formula. The laboratory findings for all 36 children were within normal limits. There were no significant differences between donors and recipients. Despite severe alteration of renal function before the laser treatment (anuria-polyuria) no long-term impairment of renal function could be detected in any of the 18 twin pairs.

Renal function during and after treatment for acute lymphoblastic leukemia in children

Renal function tests (cystatin C, serum and urine creatinine, creatinine clearance, serum and urine beta(2)-microglobulin, microalbuminuria, osmolality) were performed in 21 children at the diagnosis and during the treatment for acute lymphoblastic leukemia (ALL) (group I) and in 37 children (group II) treated for ALL 3.9+/-3.7 years before the study. The results were compared to 20 healthy children. Mean values of renal tests were in normal range at all points of analysis in groups I and II compared to the control group. Transitory higher cystatin C values (but in normal range) were observed after methotrexate administration and after the end of treatment. Deteriorated renal function was observed in one child during the treatment (after each protocol) and in five children treated previously for ALL. In conclusion, combined treatment for ALL is not associated with severe or long-term impairment of renal function.

Palliative Care: More than Just Care from a Friendly Relative

### Background: In patients with lupus nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. No clinical or laboratory markers have to date been shown to reliably portend renal prognosis, in particular renal function impairment. ### Objectives: To investigate whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function. ### Methods: Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Université catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3--26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline and repeat biopsies. We defined acute glomerular lesions as cellular proliferation, fibrinoid necrosis or karyorrhexis, cellular crescents, hyaline thrombi or wire loops, and leucocyte infiltration, and chronic glomerular lesions as glomerular sclerosis and fibrous crescents, in alignment with the NIH activity and chronicity indices. Similarly, we defined acute tubulointerstitial lesions as mononuclear cell infiltration and chronic tubulointerstitial lesions as interstitial fibrosis and tubular atrophy. ### Results: Despite a moderate correlation between urinary protein/creatinine (U-P/C) ratios and AI scores at repeat biopsy (r=0.48; P=0.001), ten patients (23.8%) with U-P/C ratios \<1.0 g/g still had a high degree of histological activity (AI score \>3). High AI scores in repeat (but not baseline) kidney biopsies were associated with an increased probability and/or shorter time to renal relapse (N=11) following the repeat biopsy (HR: 1.2; 95% CI: 1.1--1.3; P=0.007), independently of proteinuria levels. This association remained significant for the NIH activity index items within the glomerular but not the tubulointerstitial compartment of the kidney biopsies. High NIH CI scores in repeat (but not baseline) kidney biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR: 1.8; 95% CI: 1.1--2.9; P=0.016) through a median follow-up time of 131.5 (IQR: 73.8--178.2) months, being the case also for acute and chronic tubulointerstitial lesions in repeat but not baseline kidney biopsies. ### Conclusion: Our results highlight the usefulness of per-protocol repeat biopsies as an integral part of the treatment evaluation, also in patients who have shown adequate clinical response. Glomerular lesions consistent with active renal disease portend LN relapses, while tubulointerstitial lesions consistent with active disease and chronic damage portent long-term renal function impairment. ### Disclosure of Interests: Ioannis Parodis: None declared, Christina Adamichou: None declared, Selda Aydin: None declared, Alvaro Gomez: None declared, Nathalie Demoulin: None declared, Julia Weinmann-Menke: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Farah Tamirou: None declared

Renal vein thrombosis: A 10-year review

Purpose: Renal vein thrombosis (RVT) is a rare cause for pediatric surgical consultation. The purpose of this study is to review the Montreal experience in the 1990s with RVT. Methods: A retrospective chart review was conducted from 1990 through 1999. Results: Twenty-three cases were identified by Duplex ultrasound scan. Mean length of follow-up was 42 months. Eighty-three percent (83%) of cases were diagnosed within the first month of life. In utero thrombosis was suspected in 22% and was associated with caval thrombosis and factor V Leiden. Known risk factors were present in 87%. The “diagnostic triad” of flank mass, gross hematuria, and thrombocytopenia was present in only 13% at the time of diagnosis. Long-term renal function impairment was detected in 100% of those who did not receive heparin, and in 33% of those who did receive heparin. No patient required dialysis. One patient required nephrectomy for recurrent pyelonephritis. Conclusions: RVT occurs more commonly than anticipated. Because the “classic” triad of signs usually is absent at presentation, the presence of either a flank mass, hematuria, or thrombocytopenia in a patient with risk factors should prompt investigation for RVT. Factor V Leiden is a risk factor for in utero RVT. Anticoagulation improves renal outcome. Patients with RVT require long-term follow-up. J Pediatr Surg 35:1540-1542. Copyright © 2000 by W.B. Saunders Company.

Les troubles mictionnels persistant après traitement d'une valve de l'urètre postérieur: incidence et sémiologie

Micturition disorders were studied retrospectively in a series of 165 children over a period of 15 years. Among patients without lesions of the upper tract at the time of diagnosis (group A, n = 131), 18(14%) had persistant nocturnal and diurnal enuresis: one urethral stenosis and six vesicoureteric reflux required surgery: three experienced persistent pollakiuria and enuresis. Among patients with upper urinary tract damage at the time of diagnosis (group B, n = 34), seven presented with recurrent urinary tract infection, five with nocturnal and diurnal enuresis and three with urolithiasis. In the long term, only 52% of them had normal renal function and two were successfully transplanted. Micturition disorders following treatment of posterior uretral valves are frequent and usually related to the so-called valve bladder syndrome. Iatrogenic complications and mortality rate have dramatically decreased during the recent years but long-term renal function impairment remains the most critical problem.

Evaluation of late nephrotoxicity in long-term survivors of Hodgkin's disease.

Chemotherapy (Ctx) and/or radiotherapy (Rtx) are effective in the treatment of Hodgkin's disease (HD) but potentially involve late toxicities, including nephrotoxic side effects. Therefore a follow-up study has been performed to screen patients for late signs of an impaired tubular or glomerular function and to correlate data of renal function with type of therapy and cumulative doses of cytotoxic agents applied. 81 patients in complete remission for at least 2 years and a median follow-up of 96 (39-304) months, and 53 controls were examined. Clinical routine parameters such as creatinine and electrolytes were determined. A differentiation of proteinuria into the albumin, high molecular weight (HMW) and low molecular weight (LMW) fractions made it possible to assess glomerular and tubular function based on the LMW/HMW ratio. The structural protein fibronectin served as an additional, sensitive marker of glomerular integrity. Routine parameters of kidney function did not show any signs of late nephrotoxicity. However, patients treated for HD had a higher ratio of LMW/HMW in comparison to the group of healthy volunteers (p < 0.01), indicating subclinical tubular renal damage. When the cutoff for tubular damage was defined as LMW/HMW > 1.5, 50% of the patients treated with combined modality, and 42 and 37% of the patients with Ctx or Rtx alone had subclinical tubular alterations, respectively. A tendency towards a higher prevalence of subclinical tubular changes was observed in patients with higher cumulative doses of methotrexate or ifosfamide and in patients with combined Ctx and Rtx with radiation fields involving the renal area. Changes in glomerular function were not observed. It is concluded that treatment of HD is not associated with clinically apparent long-term impairment of renal function but can lead to subclinical alterations. Further clinical implications of these subclinical tubular alterations cannot be assessed at present. A differentiation of proteinuria does not have to be performed routinely but might be useful in the follow-up of selected patients with an increased risk.