Are prediction equations for glomerular filtration rate useful for the long-term monitoring of type 2 diabetic patients?

Background. The aim of this study was to compare the accuracyof prediction equations [modification of diet in renal disease(MDRD), simplified MDRD, Cockcroft–Gault (CG), reciprocalof creatinine and creatinine clearance] in a cohort of patientswith type 2 diabetes. Methods. A total of 525 glomerular filtration rates (GFRs) using¹²⁵I-iothalamate were carried out over 10 years in 87 type 2diabetic patients. Accuracy was evaluated at three levels ofrenal function according to the baseline values obtained withthe isotopic method: hyperfiltration (GFR: >140 ml/min/1.73m²; 140 isotopic determinations in 27 patients), normal renalfunction (GFR: 140–90 ml/min/1.73 m²; 294 isotopic determinationsin 47 patients) and chronic kidney disease (CKD) stages 2–3(GFR: 30–89 ml/min/1.73 m²; 87 isotopic determinationsin 13 patients). The annual slope for GFR (change in GFR expressedas ml/min/year) was considered to ascertain the variabilityin the equations compared with the isotopic method during follow-up.Student's t-test was used to determine the existence of significantdifferences between prediction equations and the isotopic method(P < 0.05 with Bonferroni adjusted for five contrast tests). Results. In the subgroup of patients with hyperfiltration, aGFR slope calculated with ¹²⁵I-iothalamate –4.8 ±4.7 ml/min/year was obtained. GFR slope in patients with normalrenal function was –3.0 ± 2.3 ml/min/year. In bothsituations, all equations presented a significant underestimationcompared with the isotopic GFR (P < 0.01; P < 0.05). Inthe subgroup of CKD stages 2–3, the slope for GFR with¹²⁵I-iothalamate was –1.4 ± 1.8 ml/min/year. Thebest prediction equation compared with the isotopic method provedto be MDRD with a slope for GFR of –1.4 ± 1.3 ml/min/year(P: NS) compared with the CG formula –1.0 ± 0.9ml/min/year (P: NS). Creatinine clearance presented the greatestvariability in estimation (P < 0.001). Conclusions. In the normal renal function and hyperfiltrationgroups, none of the prediction equations demonstrated acceptableaccuracy owing to excessive underestimation of renal function.In CKD stages 2–3, with mean serum creatinine 133 µmol/l(1.5 mg/dl), the MDRD equation can be used to estimate GFR duringthe monitoring and follow-up of patients with type 2 diabetesreceiving insulin, anti-diabetic drugs or both.     

Time course of inulin and creatinine clearance in the interval between two haemodialysis treatments

BACKGROUND: Urinary volume of haemodialysis patients with residual renalfunction increases during the interdialytic interval. The contributionof GFR to this change in water and solute excretion has notbeen quantified in detail. The creatinine clearance (Cl^c) asa determinant of the GFR may overestimate GFR caused by thetubular secretion of creatinine. Cimetidine has been used toinhibit the secretion of creatinine in non-dialysed patients.No data are available on its usefulness in haemodialysis patients. METHODS: Two identical interdialytic intervals (DI) of 3 days (DI-1,DI-2) were investigated in 11 patients. The interval betweenDI-1 and DI-2 was 1 week. During DI-2 cimetidine 800 mg dailywas administered. Each DI was divided in four urine-collectionperiods. RESULTS: The water and solute excretion in DI-1 and DI-2 were similar.Urinary production increased from 0.37 ±0.30 ml/min to0.66 ±0.33 ml/min (P<0.05), inulin clearance (C1¹)increased from 1.8±1.1 ml/min to 2.7 ± 1.2 ml/min(P<0.05), fractional sodium excretion from 9.0 ± 5.7%to 14.5 ± 9.0% (P<0.05). In contrast to Cl_i;; theCl_c showed no increase during the interdialytic interval bothin DI-1 and DI-2. The overestimation of GFR by creatinine (Cl_i– Clⁱ) decreased during DI-1 from 1.35 ±1.69 ml/minto 0.26 ± 0.60 (P<0.05) and during DI-2 from 1.01±1.33 ml/min to 0.10 ± 0.67 (P<0.01). The ratioCl^c/Clⁱ decreased during DI-1 from 1.78 ± 0.53 to 1.09± 0.19 (P< 0.01) and during DI-2 from 2.02 ±1.13to 1.05 ± 0.30 (P<0.01). All parameters were not differentbetween the comparable days of DI-1 and DI-2. CONCLUSION: We conclude that the urinary volume in the interdialytic intervalis directly related to changes in GFR. During the interdialyticinterval GFR increased and tubular secretion of creatinine decreased.The administration of cimetidine did not improve the accuracyof Cl_c as a measurement of GFR in end-stage renal failure.     

Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis

The renal effects of low-dose cyclosporin A (CsA) treatmentin severe psoriasis was investigated in 10 patients treatedwith a mean CsA dose of 3.23 (range 1.94–4.10) mg/kg/dayfor 12 months. The psoriasis area and severity index was reducedby 63–76%. Ambulatory GFR (iothalamate-¹²⁵I) ERPF (hippuran-¹³¹),RVR and MAP were examined at 3-months intervals. A control renalbiopsy was performed shortly before treatment start and a secondbiopsy was taken after 12 months of therapy. GFR was slightlybut significantly reduced after 6 and 9 months; after 12 monthsthe decrease was not significant (121.0±7.6 versus 115.2±7.8ml/min/l.73M P>0.10). After 12 months serum creatinine increasedfrom 82±4 to 94±7 µmol/litre (P<0.05while an insignificant increase of ERPF was seen and FF decreasedfrom 0.29±0.01 to 0.26±0.01 (P<0.05). MAP remainedunchanged. GFR and serum creatinine correlated significantlywithin each 3-month interval. A slight de novo interstitialfibrosis was seen in the second biopsy in 4 of 10 patients receivinga mean CsA dose of 3.2–4.1 mg/kg/day. In three of thesepatients a concomitant rise in serum creatinine was seen. In conclusion, low-dose CsA was associated with reversible fallin GFR and potentially progressive structural changes not alwaysaccompanied by corresponding functional alterations. One shouldconsider reducing the daily dose of CsA to 3.0 mg/kg body- weightor less in CsA therapy up to 1 year.     

Constant infusion clearance is an inappropriate method for accurate assessment of an impaired glomerular filtration rate

Recently renewed interest has been focused on constant infusionclearance to assess GFR accurately. In this study we comparedGFR and ERPF calculated from the constant infusion method (CIM= I x V/P) with that calculated from the standard method (StM= UxV/P), in 100 patients with renal disease who were subdividedin four groups according to their GFR-StM (<30;30–60;60–90; >90 ml/min). After a priming dose, a constantinfusion of ¹²⁵I-iothalamate (=GFR) and ¹³¹I-hippurate (=ERPF)was started at 9 a.m. The infusion rates were individually adjustedto the GFR which was approximated from the serum creatinineconcentration. After a 90-min equilibration period, GFR-StMand ERPF-StM were determined for two 2-h periods. These valueswere compared with GFR-CIM and ERPF-CIM calculated from theplasma concentration of the respective tracers at the end ofeach 2-h period (=210 and 330 min). In the patient group with GFR-StM <30 ml/min, the ¹²⁵I-iothalamateplasma concentration increased progressively over time. Consequently,average GFR-CIM at 210 min (34.2, SE±2.1 ml/min) washigher than the GFR-CIM at 330 min (31.9, SE±2.0 ml/min;P<0.001). In addition both values were significantly higherthan the corresponding GFR-StM values (18.1±2.4 and 15.3± 1.6 ml/min respectively). In the two patient groupswith GFR-StM > 60 ml/min, the ¹²⁵I-iothalamate plasma concentrationdecreased progressively over time. Consequently in both groupsGFR-CIM at 210 min was significantly lower than GFR-CIM at 330min. In all groups the ¹³¹I-hippurate plasma concentrationswere constant during the second 2-h period. Because constantplasma concentrations of ¹²⁵I-iothalamate are not obtained duringa 330 min period and GFR-CIM overestimates GFR-StM in patientswith low GFRs, we conclude that the constant infusion techniqueis not a valid method to assess GFR accurately if renal functionis impaired.     

Sequential analysis of variation in glomerular filtration rate to calculate the haemodynamic response to a meat meal

BACKGROUND: The renal haemodynamic response to a meat meal is usually measuredas either filtration capacity (maximal achieved GFR), or renalreserve (maximal GFR increase over baseline), or percent renalreserve (maximal GFR increase as a percentage of baseline).The time-course of GFR response to a meat meal varies in differentindividuals as the peak GFR tends to occur late in renal disease.This study proposes a new method to measure the GFR responseindependently of differences in peaking time. METHODS: The study is based on measurement of GFR (inulin clearance,ml/minx1.73 m² BSA) in three 30-min pre-meal clearance periods(baseline) followed by analysis of the GFR changes for up to180 min (four 30-min and one 60-min clearance periods) aftera meat meal (2 g of protein/kg of BW as red cooked meat). Datawere analysed from 85 healthy people (GFR100) and 273 individualswith renal disease (RD) who were divided into three groups basedon their baseline GFR (RD1, n=115, GFR 99–66; RD2, n=85,GFR 65–33; RD3, n=73, GFR<33). RESULTS: In healthy people after the meat meal GFR peaked between 30and 60 min and returned to baseline by 120 min. In the threeRD groups GFR peaked later than in healthy people (P<0.001)and remained higher than baseline for up to 180 min (P<0.001).Cumulative post-meal GFR changes, calculated as cumulative GFRincrease over baseline up to 120 min after meal (ml/120minx1.73m²BSA), were significantly different (P<0.01) in the four groups(healthy people, 937±141; RD1, 1222±141; RD2,587±104; RD3, 361±89). Interindividual variabilityin cumulative GFR increase was only partially explained by thevalue of nitration capacity (r²=0.285), renal reserve (r²=0.640),and percent renal reserve (r₂=0.175). CONCLUSIONS: The data indicate that commonly used parameters are poor indicesof the actual total time-course of the renal response to a proteinload.     

Contrasting Effects of Acute Angiotensin Converting Enzyme Inhibitors and Calcium Antagonists in Transplant Renal Artery Stenosis

Deterioration of renal function is a major concern during treatmentby converting enzyme inhibitors of hypertensive kidney recipientswith transplant renal artery stenosis. However, there has beenno assessment of the frequency of this complication and itsspecificity for converting enzyme inhibitors as compared toother antihypertensive drugs. The effect of acute administrationof captopril on mean arterial pressure, glomerular filtrationrate (GFR) (creatinine clearance) and effective renal plasmaflow (clearance of ¹³¹I-hippuran) was assessed in eight hypertensivepatients with transplant renal artery stenosis. Captopril induceda decrease in mean arterial pressure (128±6–121±7mmHg) and a reduction in GFR (59±8–44±8ml/minper 1.73m², P<0.05). The decrease in GFR was observed inseven out of eight patients and varied between 0% and 100% ofthe pre-captopril value. Effective renal plasma flow was maintained(157±47–141 ±24m1/min per 1.73m²) and filtrationfraction decreased by 15±7%. The effect of captoprilwas compared to that of nifedipine (N=20 mg) in four patients.Despite a larger decrease in mean arterial pressure (130±7–109±10mmHg), no reduction in GFR was observed (68±13–71.4±8).Effective renal plasma flow was unchanged and filtration functionslightly increased. Surgical or percutaneous transluminal angioplastyin five patients suppressed the captopril-induced decrease inGFR. We conclude that (1) renal insufficiency induced by convertingenzyme inhibitors is frequent in severe transplant artery stenosis;(2) renal function is well maintained during nifedipine-inducedreduction in blood pressure; (3) renal insufficiency inducedby converting enzyme inhibitors is not due to reduction of systemicblood pressure but to intrarenal effects of angiotensin II.     

Effects of cyclosporin A withdrawal on renal function and renal stimulation in liver transplant patients treated with triple-drug immunosuppression for over 2 years

The influence of CsA withdrawal on the glomerular filtrationrate (GFR) and the effective renal plasma flow (ERPF) was prospectivelystudied in nine stable liver transplant recipients. Before CsAwithdrawal (test 1), and 6 months thereafter (test 2) the renalfunction was determined by measuring GFR and the ERPF with ¹²⁵I-iothalamateand ¹³¹I-hippuran respectively. The renal function was alsostimulated with dopamine, with an amino-acid infusion and acombination of both. After CsA withdrawal the GFR increased,median from 74 ml min^–1 to 90 ml min^–1, (P<0.04).The ERPF also increased, median from 310 ml min^–1 to 380ml min^–1, (P<0.03). In test 1 as well as in test 2the renal function could be stimulated, especially with dopamine.GFR and ERPF improved, even after more than 2 years of CsA treatment.These results suggest that long-term CsA treatment impairs therenal function, though in these liver transplant patients CsAtreatment did not prevent afferent and efferent arteriolar vasodilatationafter renal stimulation. This reversible intrarenal vasoconstrictionduring CsA treatment may predict renal improvement after CsAwithdrawal.     

Correlation between glomerular morphology and renal haemodynamic response to amino-acid administration in patients with IgA nephropathy

RATIONALE.: To establish relationship, if any, between renal morphologyand renal haemodynamic response to amino acids. DESIGN AND METHODS.: We investigated the correlation between renal haemodynamic regulationand morphology in a group of 15 patients with primary IgA nephropathy(IgAN) (age 26±2 years, BMI 24.4±1, GFR 64±5ml/min, RPF 377±34 mI/mm, FF 0.17±0.02). Twelvenormal subjects (age 30±3 years, BMI 24±1, GFR82±6 ml/min, RPF421±42 ml/min, FF 0.19±0.02)were studied as controls. IgA patients were divided into twogroups according to the histological staging of glomerular lesions:group I (n=7) stage II, and group II (n=8) stage III–IV. RESULTS.: In the basal state GFR was similar in the two groups and averaged64±9 and 64±6 ml/mm respectively. In contrast,FF was significantly lower in group II(0.14±0.01) (P<0.05)in comparison to group I (0.21±0.03) and controls (0.19±0.02).In order to evaluate the renal functional reserve, all studygroups underwent to an intravenous amino-acid infusion designedto increase plasma amino acid levels twofold (total from 2096±145to 4301±221 µmol/l in IgA nephropathy patientsand from 2272±83 to 3844±238 µmol/l in controls).In response to amino-acid infusion, GFR rose significantly ingroup I (GFR 20±2% and RPF 37±4% versus basal)and controls (GFR 20±2% and RPF 20±3% versus basal)(both P<0.01 vs basal). In contrast, in patients with moresevere glomerular lesions (group II) neither GFR nor RPF rosesignificantly (GFR –1±4% and RPF –8±6%versus basal) (P NS versus basal, P<0.01 versus group I andcontrols). CONCLUSIONS.: The data show that in IgA nephropathy: severe forms of glomerularlesions are associated with a complex alteration of glomerularhaemodynamic regulation, characterized by lower basal FF andloss of haemodynamic response to hyperaminoacidaemia.     

Kidney transplantation decreases the tissue level of advanced glycosylation end-products

We have studied the effect of chronic renal failure (CRF) andkidney transplantation on advanced glycosylation end-products(AGE) measured as collagen-linked fluorescence (CLF) in theskin and peritoneum of non-diabetic patients. Of 34 patientswith CRF, 18 were studied before the commencement of peritonealdialysis (CRF group), and 16 were studied 5–31 weeks afterkidney transplantation (transplant group). The control groupconsisted of 24 patients with normal renal function. Skin CLFin the CRF group (20.9 ± 2.02 U/mg) was higher than inthe control (8.52±1.08 U/mg, P = 0.0001) and transplantgroups (10.7 ± 2.43 U/mg, P=0.003). Peritoneal CLF inthe CRF group (30.5 ± 5.64 U/mg) was higher than in thecontrol group (16.1 ±2.25 U/mg, P=0.031) but was notdifferent from the transplant group (19.4 ± 3.66 U/mg,P=0.11). Peritoneal CLF of control and transplant groups werenot different (P= 0.45). The results of this study suggest thatrestoration of renal function affects tissue AGE levels.     

Age as a determinant of glomerular filtration rate in non-insulin-dependent diabetes mellitus

BACKGROUND: The level of glomerular filtration rate (GFR) and its determinantsin non-insulin-dependent diabetes mellitus (NIDDM) are currentlycontroversial. DESIGN OF THE STUDY: We measured GFR and effective renal plasma flow (ERPF) in 121consecutive NIDDM without evidence of overt diabetic nephropathy.Age varied from 28 to 70 years, 61.2% were women and known durationof NIDDM was 0–37 years. Hypertension was detected in36.4% of patients and 47.8% had microalbuminuria. RESULTS: An inverse correlation was found between GFR and age, but notwith known duration of NIDDM. It was a weak correlation (r=–0.41)but statistically significant (P<0.001). The other variablesconsidered were not significant by multiple stepwise regressionanalysis, but patients with lower GFR tended to have diabeticretinopathy more frequently. GFR was lower in hypertensive comparedto normo tensive patients (123±28.4 versus 136±32.5ml/min/1.73 m²; P<0.05), but was not different between patientswith normal and elevated albumin excretion rate. ERPF also hadan inverse correlation with age (r=–0.45, P<0.001). CONCLUSION: We conclude that (i) age should be considered as a confoundingvariable when evaluating GFR in patients with NIDDM, and (ii)the age-dependent decline in GFR may mask hyperfiltration inthe early stages of diabetic nephropathy in NIDDM.     

Reduction of Blood Pressure Retards the Progression of Chronic Renal Failure in Man

The effect of blood pressure reduction on the progression rateof chronic renal failure (CRF) was studied in 28 patients withCRF of diverse aetiology entering a prospective study (observationtime 7–24 months, mean 16 months). Endogenous creatinineclearance was 12–66 ml/mm (mean 30±3 ml/mm). Weaimed to keep the blood pressure below 160/90 mmlHg. Dietaryprotein was not restricted. The progression rate of CRF wasassessed from the regression coefficients of the regressionsof creatinine clearance and the inverse of s-creatinine, respectively,on time. Progression rate and the means of all recordings ofmean arterial blood pressure (MAP) and urinary protein excretion,respectively, in each patient during the prospective phase werecompared with retro spective data from the proceeding period(observation time 4–25 months, mean 19 months). The patientsreceived various combinations of antihypertensive drugs includingdiuretics, beta-blockers and vasodilatory drugs. In 19 patientsMAP decreased from 109±2 to 102±2 mmHg (groupI), whereas MAP increased from 105±2 to l08±2mmHgin nine patients (group II). In group I proteinuria was significantlylower (P<0.05) and the progression of CRF was approximately50% slower (P.<0.01) in the prospective phase than in theretrospective phase; no changes were observed in group II. Calculatedfor all patients, significant correlations were observed betweenthe change in MAP and the change in progression rate and proteinexcretion, respectively. These results indicate that loweringof blood pressure results in decreased proteinuria and retardationof the progression of CRF irrespective of the aetiology.     

Cyclosporin does not inhibit the tubular secretion of creatinine

BACKGROUND: The immunosuppressive drug cyclosporin is known to impair renalfunction. The degree of renal dysfunction is usually estimatedfrom the clearance of creatinine (C_Cr). Theoretically however,a fall in C_Cr can be caused by a decrease of GFR, an inhibitionof the tubular secretion of creatinine, or the combination ofboth. CsA has convincingly been shown to decrease GFR, but detailedinformation on the effects of CsA on tubular secretion of creatinineis lacking. METHODS: We performed two studies to investigate the influence of CsAon tubular creatinine secretion. In study A we simultaneouslymeasured C_Cr and GFR (using inulin) immediately before and 4weeks after cessation of CsA therapy in 17 renal transplantpatients. In study B, the rise in serum creatinine after administrationof cimetidine, which blocks the tubular secretion of creatinine,was compared in renal transplant patients treated with eitherCsA (in whom secretion might already be inhibited) or azathioprine. RESULTS: Study A: After cessation of CsA there was an increase of GFR(54±15 vs 63± 16 ml/min/1.73 m²; P>0.01) andof C_Cr (71±21 vs 82±23 ml/min/1.73 m²; P>0.01),but the ratio between C_Cr and GFR (a measure of the relativecontribution of tubular secretion to the clearance of creatinine)did not change significantly (1.33±0.21 vs 1.32±0.30).Study B: In nine couples of patients matched for GFR the relativerises in serum creatinine after administration of cimetidinewere 26±21% and 22±7% for the CsA and azathioprinetreated patients respectively (NS). CONCLUSIONS: CsA does not substantially inhibit the tubular secretion ofcreatinine. A rise in serum creatinine after administrationof CsA can thus be attributed completely to a fall in GFR.     

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis

Aplastic bone disease (ABD) is a common form of renal osteodystrophyand is characterized by a defect in bone matrix formation andmineralization without an increase in osteoid thickness. Theprevalence and pathogenesis of ABD in predialysis patients islargely unknown. We prospectively studied 92 unselected predialysispatients with a creatinine clearance <10 ml/min/1.73 m² anda mean age of 45±2 years (61 M, 31 F). None of the studypatients had received any form of vitamin D therapy, and CaCO₃was the primary phosphate binder. Aplastic bone disease wasobserved in 30 (32%) patients. Stainable bone aluminium surfacewas <3% in all ABD patients. Patients with ABD were older(52±3 versus 42±2 years; P<0.01) and had reducedserum intact PTH compared to non-ABD patients (199±25versus 561 ±87 pg/ml; P<0.001). Patients with diabetesmellitus showed lower PTH values (179±31 versus 432±62pg/ml; P<0.001) and a lower incidence of advanced by chperparathyroidismbone lesions (16% versus 46%; P<0.05) than non-diabetic patients.However, diabetes was not clearly associated with low bone turnoverdisease (56% in diabetics versus 41% in non-diabetics; P=0.1). A second bone biopsy was obtained in eleven ABD patients aftera period of 16.6±2.2 months on maintenance dialysis witha dialysate calcium of 7 mg/dl. Bone histology was unchangedin 10 patients, and one evolved to mild hyperparathyroidism.Trabecular bone volume did not change (22.7± 1.7 versus20.7±1.7%), and the stainable bone aluminium surfaceremained <3%. In summary, ABD not associated with positive histological stainingfor aluminium is a common finding in asymptomatic end-stagerenal failure patients in the Canary Islands. Older age andrelatively low PTH values are associated with this form of bonedisease. After a period of 12–36 months of dialysis, progressiveosteopenia and other clinical problems do not occur.     

Thresholds of serum calcium oxalate supersaturation in relation to renal function in patients with or without primary hyperoxaluria

Systemic oxalosis is a constant feature in patients with primaryhyperoxaluria type 1 (PH1) and chronic renal failure (CRF) andis not prevented by regular dialysis (RDT), because removalcannot keep up with retention and overproduction of oxalate.These patients are candidates to kidney and/or liver transplantation,which should be ideally planned prior to the development ofoxalosis. However, methods to detect the presence and extentof oxalosis are invasive and poorly reproducible, and only indirectapproaches are feasible. Because supersaturation of body fluidsis an essential condition for oxalotic deposits to form, wehave assessed serum calcium oxalate saturation (ß_Caox)in 12 patients with PH1 and 26 with PH1-unrelated renal diseasesand varying degrees of CRF. Nineteen healthy individuals weretaken as controls. ß_Caox was closely dependent onoxalate serum levels. Serum oxalate and ß_Caox wereincreased in patients with CRF as compared to controls, andwere inversely related to GFR, assessed as creatinine clearance.However, at any level of GFR, both were always greater in PH1patients. From the slopes of the regression of ß_Caoxover CICr, saturation was predicted to be obtained at CICr ranging24–34 and 8–11 ml/min/1.73 m² in PH1 and non-PH1patients respectively. Based on the dependence of ß_Caoxon oxalate, saturation was associated with serum oxalate between44 and 46 µmol/l, irrespective of either the prevailingGFR or the underlying disease. These simple procedures representa valuable non-invasive tool to define the risk of systemicoxalosis and may assist in timing of transplantation.     

Progression rate to end-stage renal failure in non-diabetic kidney diseases: a multivariate analysis of determinant factors

BACKGROUND.: The respective contribution of the type of nephropathy, gender,and proteinuria, and of the potentially alterable factors bloodpressure level and daily protein intake on the rate of progressionin non-diabetic renal diseases is debated. METHODS.: We retrospectively analysed the influence of primary renal disease,gender, urinary protein excretion, mean arterial pressure (MAP),and dietary protein intake on the rate of decline in creatinineclearance (Ccr) in 159 adult patients with well-defined nondiabetickidney diseases. All patients had been followed from a baselineCcr of 40–50 ml/min/1.73 m² until endstage renal diseaseand need for dialysis. RESULTS.: Mean (±SD) Ccr (ml/min/1.73 m²/year) was 9.9±6.5in 51 patients (45 males) with chronic glomerulonephritis, 6±2.5in 50 patients (26 males) with polycystic kidney disease, 5.5±2.4in 17 patients (16 males) with hypertensive angionephrosclerosis,and 3.9±2 in 41 patients (21 males) with chronic tubulointerstitialnephritis. Ccr was higher in males than in females (7.5±5.2versus 4.8±2.5; P <0.001). Linear regression analysisof the whole population disclosed a strong relationship betweenCcr and proteinuria (r² = 0.23; P < 0.001), and a weak relationshipbetween Ccr and protein intake (r² = 0.03; P = 0.02), but norelationship between Ccr and MAP (r² = 0.01; P = 0.23). Stepwisemultiple regression analysis identified the type of nephropathy,gender, and proteinuria as independent predictive factors ofprogression; however, these factors together accounted for only36% of the variation in Ccr, suggesting the contribution ofother yet unidentified factors. CONCLUSIONS.: Primary kidney disease and urinary protein excretion (reflectingthe severity of renal disease in individual cases) appear asthe major determinants of the rate of progression, with fasterprogression in males in all types of nephropathy, whereas potentiallyalterable factors such as blood pressure and protein intakehad only a modest influence in the range of values observedin our patients.     

Hyperuricaemia in cyclosporin-treated patients: a GFR-related effect

BACKGROUND: Hyperuricaemia is a well known side-effect of cyclosporin A(CsA) treatment. The pathogenic mechanisms, however, remaincontroversial. There is no convincing evidence that hyperuricaemiais due to CsA-induced, impaired tubular handling of uric acid.The impact of diminished GFR in this particular context hasnever been investigated. METHODS: We prospectively studied plasma uric acid, inulin clearances,and fractional clearances of uric acid in two groups of CsA-treatedpatients (bone-marrow transplant patients, n=50; renal transplantpatients, n=32), and one healthy control group without CsA (livingrelated kidney donors, n=28). Bone-marrow transplant patientswere examined before transplantation and 6, 12, 18, 24 monthsafter transplantation, renal transplant patients 1 year aftertransplantation, and living related kidney donors before and1 year after unilateral nephrectomy. RESULTS: After 1 year of CsA treatment, hyperuricaemia was found in 36%of bone-marrow transplant patients and in 53% of renal transplantpatients. Thirty per cent of living related kidney donors wereborderline hyperuricaemic 1 year after unilateral nephrectomy.The fractional clearance of uric acid, measured serially inbone-marrow transplant patients did not change significantlyover time; it was, however, slightly higher during CsA treatmentthan after CsA withdrawal. Moreover, the bone-marrow transplantpatients' fractional clearance of uric acid was not statisticallydifferent from the renal transplant patients' and the livingrelated kidney donors' (values 1 year after transplantation/unilateralnephrectomy: bone-marrow transplant patients, 15.3±2.3%;renal transplant patients, 11.9±0.9%; living relatedkidney donors, 11.1±0.8%). The GFR at 1 year, measuredby inulin clearance, was identical in the CsA-treated groupsand slightly higher in the living related kidney donors (bone-marrowtransplant patients, 51±6 ml/min per 1.73 m² renal transplantpatients, 49±3 ml/min per 1.73 m² living related kidneydonors, 61±2 ml/min per 1.73 min²). CONCLUSIONS: There is no evidence for impaired tubular handling of uric acid,induced by a CsA-specific tubulotoxic effect. Hyperuricaemiain CsA-treated transplant patients can therefore be attributedto the cyclosporin associated decrease of GFR.     

Urinary prostaglandins (PGE2 and PGI2) in hyporeninaemic hypoaldosteronism in diabetic patients with chronic renal failure

The present work studies the urinary excretion of PGE₂ and PGI₂(6-keto PGF 1) in 11 insulin-dependent diabetic patients withchronic renal failure with a glomerular filtration rate of 33.9±9.03 ml/min who had hyporeninaemic hypoaldosteronismto evaluate the influence of these prostaglandins on the appearanceof this latter process. The results obtained in this group ofpatients were compared with those of a control group of healthyindividuals, another group of nine non-diabetic patients withCRF, and a last group of eight insulin-dependent diabetic patientswith normal renal functión to evaluate to what extentthe possible variations in prostaglandin excretion could berelated to the diabetes, CRF, or a conjunction of both processes. The results of the groups of diabetic patients with CRF wereC_cr 33.9 ±9.03 ml/min, decreased (P< 0.0001) withrespect to the control group and with no difference with theCRF group without diabetes; plasma potassium (4.7 ±0.4mEq/l), increased P<0.005) with respect to the values foundin the control group; plasma bicarbonate (17.8 ± 1.8mEq/l), decreased (P< 0.005) with respect to the controlgroup and also, though not significantly, with respect to thegroup of non-diabetic patients with CRF. Plasma aldosterone(pg/ml): resting 44.3±14.9; standing 65.7 ±63.5and post-frusemide 65.5 ±58.6, decreased (P<0.01)with respect to the other three groups. Plasma renin activity(PRA) (ng/ml/h): resting 0.34±0.3; standing 0.6 ±0.4, post-fmsemide 0.9 ±0.5, decreased significantlywith respect to the other three groups. PGE₂ (pg/mg Cr): basal1720±397; post-frusemide 2636±462, increased (P<0.05)with respect to the control group and that of the diabetic patientswithout CRF, but with no differences compared with the non-diabeticpatients with CRF. PGI₂ (pg/mg cr): basal 369 ±45 andpost-frusemide 699 ± 103, increased (P<0.01) withrespect to the controls and diabetic patients with normal renalfunction and with no differences compared with the non-diabeticpatients with CRF. Our findings indicate that patients with diabetes mellitus andCRF showing hyporeninaemic hypoaldosteronism have high urinaryexcretion of PGE₂ and PGI₂. The increase in the urinary prostaglandinsis related to CRF. The data rule out the hypothesis that thehyporeninaemic hypoaldosteronism of these patients is due toa deficit of prostaglandins.     

Renal function on and off lithium in patients treated with lithium for 15 years or more. A controlled, prospective lithium-withdrawal study

BACKGROUND.: Controversy remains over the magnitude and reversibility ofreduced renal function in long-term lithium patients. METHOD.: Thirteen patients with 18 years (range 15–24) on lithiumdiscontinued the treatment, and were re-examined twice after5 and 9 weeks (4–16) off lithium. They were compared toa non-lithium psychiatric control group, matched for age andsex. RESULTS.: Glomerular filtration rate (GFR) tended to improve from 69 (39–96)to 74 (39–94) ml/min/1.73 m² BSA, P=0.057, which was notsignificantly different from 78 (61–106 ml/min per 1.73m² BSA in the controls. Reduced GFR was found in only two ofthe lithium patients off lithium, and in none of the controls.Maximal urinary concentrating capacity did not improve at all.It was 637 (130–875) mOsm/kg H₂O in the lithium patients,which was lower than 856 (705–1.035) mOsm/kg H₂O (P<0.01)in the controls. Two of the lithium patients had isosthenuria. CONCLUSIONS.: Lithium patients often have an irreversible, clinically importantreduction of Umax, sometimes progressing to nephrogenic diabetesinsipidus, while GFR is well preserved in most patients.     

Haemodynamic changes induced by the correction of anaemia by erythropoietin: role of antiplatelet therapy

BACKGROUND.: In a restrospective study, antiplatelet therapy has been shownto be associated with a decreased incidence of erythropoietin-inducedhypertension. In order to ascertain the role of antiplateletdrugs in the haemodynamic response to the correction of anaemiaby rHuEpo, 18 patients on chronic haemodialysis who startedrHuEpo therapy were prospectively studied. METHODS.: The subjects were randomly assigned to receive or not, one ofthe following antiplatelet drugs: ditazole (3 patients), ticlopidine(3 patients) or aspirin plus dipyridamole (3 patients). Cardiacindex (CI) by echo-Doppler, total peripheral resistance (TPR)and mean arterial pressure (MAP) were determined at baseline10 and 20 weeks following the initiation of rHuEpo therapy.rHuEpo therapy was administered subcutaneously at the same dose(40 U/kg thrice weekly) during the first 10 weeks. Ten uraemicpatients on haemodialysis who had never received rHuEpo therapyserved as the control group. RESULTS.: One patient in the group without antiplatelet drugs discontinuedthe study due to the development of severe hypertension after12 weeks on rHuEpo therapy. There were no significant differencesin the haemodynamic parameters at baseline. At 10 weeks, MAPwas higher in patients without than with antiplatelet drugsor controls untreated with rHuEpo (128.5 ± 28 versus100.6 ± 13.5 versus 98.7 ± 14 mmHg respectively,P = 0.0047), TPR was also higher in patients without antiplateletdrugs than in the 2 other groups (1919 ± 433 versus 1576± 359 versus 1418 ± 324 din.seg.cm^–5 m²respectively, P = 0.0231), but CI did not differ among the threegroups. At 20 weeks, MAP was still higher in patients withoutantiplatelet drugs than in patients with antiplatelet drugsor controls not on rHuEpo therapy respectively (112.9 ±24.6 versus 91.0 ± 9.0 versus 101.7 ± 14.1 mmHgrespectively, P = 0.075), but at this stage TPR and Cl did notdiffer among the three groups. CONCLUSIONS.: These data reinforce the previous observation that antiplatelettherapy may prevent the development of rHuEpo-induced hypertension.     

Association of chronic kidney disease with outcomes in chronic heart failure: a propensity-matched study

Background. Chronic kidney disease (CKD) is associated withincreased mortality in patients with heart failure (HF). However,its association with hospitalization in HF patients has notbeen well studied. Methods. Of 7788 patients in the Digitalis Investigation Grouptrial, 3527 had CKD, defined by an estimated glomerular filtrationrate (GFR) <60 ml/min/1.73 m² body surface area (BSA). Propensityscores for CKD were calculated using a multivariable logisticregression model and used to match 2399 pairs of patients withand without CKD. Matched Cox regression analyses were used toestimate association of CKD with outcomes. Results. All-cause hospitalization occurred in 1636 (rate, 4233/10 000person-years) and 1587 (rate, 3733/10 000 person-years)patients respectively, with and without CKD (matched hazardratio [HR] for CKD, 1.18, 95% confidence interval [CI], 1.08–1.29;P < 0.0001). Matched HR for cardiovascular and HF hospitalizationwere respectively 1.17 (95% CI, 1.06–1.28, P = 0.002)and 1.28 (95% CI, 1.13–1.45, P < 0.0001). Comparedto GFR 60 ml/min/1.73 m² BSA, HR for all-cause hospitalizationfor GFR 45–59 and <45 ml/min/1.73 m² BSA were respectively1.04 (95% CI, 0.94–1.16; P = 0.422) and 1.58 (95% CI,1.34–1.87; P < 0.0001). Similarly, HR for all-causedeath for GFR 45–59 and <45 ml/min/1.73 m² BSA wererespectively 1.03 (95% CI, 0.90–1.18; P = 0.651) and 1.70(95% CI, 1.40–2.07; P < 0.0001). Matched HR for deathdue to cardiovascular causes and progressive HF were respectively1.24 (95% CI, 1.09–1.40; P = 0.001) and 1.42 (95% CI,1.16–1.72; P = 0.001). Conclusion. CKD was associated with increased mortality andhospitalization in ambulatory patients with chronic HF, whichincreased progressively with worsening kidney function.