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Biomedical subjects

K Lhotta

Publications and source records attributed to K Lhotta.

At least 19 recordsLinked to original sources
PubMed2006

Conversion to enteric-coated mycophenolate sodium from various doses of mycophenolate mofetil: results of a prospective international multicenter trial in maintenance renal transplant patients receiving cyclosporine.

Conversion from mycophenolate mofetil (MMF, CellCept) to enteric-coated mycophenolate sodium (EC-MPS, myfortic) is safe and effective in renal transplant patients treated with the standard dose of 2 g MMF. In this 6-month, international, multicenter, open-label, single-arm trial, a large cohort of maintenance renal transplant patients receiving different doses of MMF were converted under normal clinical conditions to equimolar doses of EC-MPS. Mean calculated creatinine clearance remained stable from the time of study entry (59.6 +/- 19.7 mL/min) to the end of the study (58.3 +/- 19.8 mL/min). Adverse events were reported by 152 patients (67%), with gastrointestinal complications being observed in 45 patients (20%). Thirty-three patients (15%) experienced adverse events or infections with a suspected relation to EC-MPS, including one case of anemia and two cases of leukopenia. Eleven patients (4.9%) required a reduction in EC-MPS dose and seven patients (3.1%) permanently discontinued EC-MPS owing to adverse events. At month 6 after conversion, five patients (2.2%) experienced biopsy-proven acute rejection. There were no graft losses or deaths. These data support earlier findings that stable maintenance renal transplant patients receiving MMF with cyclosporine with or without corticosteroids can be converted to EC-MPS with no compromise in efficacy and tolerability, and no adverse effect on renal function.

Adult↗
PubMed2006

Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting.

Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia. Mutations in the sodium/glucose co-transporter SGLT2 coding gene, SLC5A2, were recently found to be responsible for the disorder. Here, we report the molecular and phenotype study of five unrelated FRG families. Five patients were identified and their family members screened for glucosuria. SLC5A2 coding region of index cases was polymerase chain reaction amplified and sequenced. Five different mutations are reported, including four novel alleles. The IVS12+1G>A and p.A102V alleles were identified in homozygosity in index patients of two unrelated families. A proband from another family was compound heterozygous for the p.R132H and p.A219T mutations, and the heterozygous p.Q167fsX186 frameshift allele was the only mutation detected in the affected individual from an additional pedigree. For the remaining family no mutations were detected. The patient homozygous for the p.A102V mutation had glucosuria of 65.6 g/1.73 m(2)/24 h, evidence of renal sodium wasting, mild volume depletion, and raised basal plasma renin and serum aldosterone levels. Our findings confirm previous observations that in FRG, transmitted as a codominant trait with incomplete penetrance, most mutations are private. In the only patient with massive glucosuria in our cohort there was evidence evocative of renin-angiotensin aldosterone system activation by extracellular volume depletion induced by natriuresis. Definite proof of renin-angiotensin aldosterone system activation in FGR should rely on evaluation of additional patients with massive glucosuria.

DNA Mutational Analysis↗
PubMed2006

Acute inflammatory syndrome induced by mycophenolate mofetil in a patient following kidney transplantation.

Mycophenolate mofetil (MMF) is increasingly used to prevent acute and chronic rejection following kidney transplantation and in autoimmune diseases. Here, we report on a patient after kidney transplantation, who developed an acute inflammatory syndrome characterized by fever and oligoarthritis within 1 week after increasing the MMF dosage. MMF was discontinued resulting in a complete resolution of the syndrome within 48 h. We demonstrated in vitro that the patient's phorbol myristate acetate (PMA-) and formyl Met-Leu-Phe (fMLP-) stimulated polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MMF. This report demonstrates that MMF can also induce acute inflammatory syndrome in patients following kidney transplantation and that this syndrome might be due to a paradox, pro-inflammatory reaction of PMNs.

Aged↗
PubMed2004

Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematosus.

We describe the case of a female patient with hereditary complete C4 deficiency and systemic lupus erythematosus. She had suffered from lupus nephritis in early childhood. At the age of 23 years she developed severe lupus with skin disease and life-threatening cerebral vasculitis. Her cerebral disease was unresponsive to high-dose steroids, intravenous immunoglobulin, fresh frozen plasma and plasma exchange. Improvement was achieved with immunoadsorption in combination with mycophenolate mofetil. The patient made a complete recovery and is maintained in complete remission on mycophenolate and low-dose steroids.

Adult↗
PubMed2004

Four consecutive renal transplantations in a patient with adenine phosphoribosyltransferase deficiency.

We report a patient with complete adenine phosphoribosyltransferase deficiency and urolithiasis, in whom 4 consecutive cadaveric renal transplantations were performed; 2,8-dihydroxyadenine crystal nephropathy recurred within weeks in the first and second graft when the patient was not treated with allopurinol immediately after transplantation. In the third graft, recurrence of disease could be prevented by immediate allopurinol treatment. This graft was lost due to chronic allograft nephropathy without significant crystal deposition. After a fourth transplantation, again without initial allopurinol, the disease recurred following an initial vascular rejection. Addition of allopurinol significantly improved renal function of the 2nd and 4th graft. This case indicates that outcome of renal transplantation in patients with adenine phosphoribosyltransferase deficiency critically depends on immediate postoperative pharmacotherapy with allopurinol, which is able to prevent 2,8-dihydroxyadenine nephropathy in the graft. Furthermore, rapid recurrence of disease without allopurinol seems to be triggered by delayed graft function and acute rejection.

Adenine Phosphoribosyltransferase↗
PubMed2003

UROMODULIN mutations cause familial juvenile hyperuricemic nephropathy.

Gout, which is commonly associated with hyperuricemia, affects 0.2% of the population. Hyperuricemia has a heterogeneous etiology that may be due to either over production and/or reduced renal clearance, of urate. In order to identify the mechanisms underlying reduced excretion of urate, we undertook positional cloning studies of familial juvenile hyperuricaemic nephropathy (FJHN), which is an autosomal dominant disorder characterized by hyperuricaemia, a low fractional renal excretion of urate, and chronic renal failure that is associated with interstitial fibrosis. The FJHN locus has been previously localized to a 22 centiMorgan interval flanked centromerically by D16S401 and telomerically by D16S3069, on chromosome 16p11-p13. This interval contains over 120 genes and we selected 13 renal expressed sequences to search for mutations in 5 unrelated FJHN families that contained 21 affected and 24 unaffected members. This revealed 5 heterozygous missense mutations (Cys77Tyr, Cys126Arg, Asn128Ser, Cys255Tyr and Cys300Gly) that altered evolutionary conserved residues in the gene encoding UROMODULIN. UROMODULIN, which is an 85 Kda glycoprotein, has roles in renal stone formation, the modulation of immune responses, and urothelial cytoprotection. The results of our studies, which have identified the gene causing FJHN, now indicate a further, novel role for UROMODULIN in urate metabolism.

Amino Acid Sequence↗
PubMed2001

Chronic renal transplantation: a model for the hyperhomocysteinemia of renal insufficiency.

Renal transplant recipients (RTR) are considered representative of patients with chronic renal insufficiency (CRI) in general with respect to both reduced, progressively declining renal function, and increased risk for cardiovascular disease (CVD). In accord with this argument, we hypothesized that total (t) plasma concentrations of the putatively atherothrombotic amino acid homocysteine (Hcy) would be equivalent in RTR and CRI patients with comparable renal function. We determined plasma tHcy, folate, pyridoxal 5'-phosphate, and B12 concentrations, in addition to serum creatinine and albumin concentrations, in 86 chronic, stable RTR, and 238 patients with CRI. Within comparable ranges of serum creatinine (i.e. RTR=0.6-4.2 mg/dl; CRI=0.7-4.1 mg/dl), tHcy concentrations did not differ between the two groups (RTR=15.0 micromol/l; CRI=14.9 micromol/l, P=0.899). ANCOVA revealed that renal function, gauged as a simple creatinine measurement, was the major independent determinant of plasma tHcy concentrations, accounting for approximately 80-90% of the total variability in tHcy predicted by the full model (i.e. full model R(2)) containing, in addition to creatinine, the seven other potential explanatory variables. If controlled trials confirm that tHcy-lowering treatment reduces CVD events rates in RTR, these results should be applicable to CRI patients in general.

Adult↗
PubMed2001

Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate.

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.

Adult↗
PubMed2001

[Pathogenesis and clinical course of hereditary nephropathies].

Hereditary diseases have to be considered in the differential diagnosis of many kidney diseases. The kidney can be affected by systemic metabolic diseases such as primary hyperoxaluria or Fabry's disease. Inborn errors of the coagulation cascade or the complement system may cause familiar forms of the hemolytic uremic syndrome. Of central interest are hereditary cystic kidney diseases with autosomal dominant polycystic kidney disease as its most prominent example. Hereditary forms of the nephrotic syndrome are usually caused by abnormalities of podocyte function. Alport's syndrome is a classical example of a basement membrane disease. Of special interest are hereditary defects in tubular transport mechanisms such as carrier defects affecting sodium reabsorption along the tubulus.

Disease Progression↗
PubMed2000

Pyuria in patients treated with indinavir is associated with renal dysfunction.

BACKGROUND: Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum. METHODS: A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls. RESULTS: Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01). CONCLUSION: Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.

Adult↗
PubMed1999

Lipoprotein(a) plasma concentrations after renal transplantation: a prospective evaluation after 4 years of follow-up.

The highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.

Adult↗
PubMed1999

Glomerular deposition of mannose-binding lectin in human glomerulonephritis.

BACKGROUND: Mannose-binding lectin (MBL), a member of the collectin family, binds to various oligosaccharides and activates the classical pathway of complement independent from C1q. At present it is unknown whether this so-called lectin pathway of complement activation plays a role in the pathogenesis of human glomerulonephritis. METHODS: Direct immunofluorescence of 84 renal biopsies using an MBL-specific monoclonal antibody and antibodies directed against IgG, IgA, IgM, C1q, C3, and terminal complement complex (TCC) was performed. Serum MBL levels of 50 patients were determined by enzyme-linked immunosorbent assay. RESULTS: MBL was detected in the glomeruli of patients with lupus nephropathy (15 of 16), membranous nephropathy (10/15), membranoproliferative glomerulonephritis type I (5/6) and anti-GBM nephritis (2/4). MBL deposition paralleled that of immunoglobulins, C1q, C3, and TCC but was less intense as compared to C1q. Focal segmental deposits of MBL were present in focal segmental glomerulosclerosis (4/6), IgA nephropathy (3/11), amyloidosis AL (1/4), and advanced renal fibrosis (2/2). Here MBL staining was identical to IgM and C3 and considered an unspecific entrapment of MBL in sclerotic lesions in these cases. No significant difference in MBL serum levels was observed between normal controls and patients with lupus nephritis, membranous nephropathy, membranoproliferative glomerulonephritis, focal segmental sclerosis, minimal change disease or IgA nephropathy. In patients suffering from membranous nephropathy with (n=10) or without (n=5) glomerular MBL deposits serum creatinine, C3, C4, serum protein, and proteinuria were not statistically different. CONCLUSION: MBL is present in the glomeruli of patients with glomerulonephritis involving deposition of IgG and activation of the classical pathway of complement. We propose that MBL binds to agalactosyl oligosaccharides of IgG that terminate in N-acetylglucosamine. The extent to which the lectin pathway of complement contributes to overall complement activation in the glomeruli remains unknown, but is likely to be marginal.

Antibodies, Monoclonal↗
PubMed1999

Thrombotic microangiopathy with renal failure in two patients undergoing gemcitabine chemotherapy.

Described here are 2 patients who developed thrombotic microangiopathy of the kidneys after receiving high cumulative doses of the new anticancer drug gemcitabine. The first patient, who received gemcitabine for treatment of a carcinoma of the pancreas, required hemodialysis for 6 months. In the second case, a woman suffering from a cholangiocellular carcinoma, end-stage renal disease was irreversible. Clinical awareness, timely detection and discontinuation of gemcitabine are mandatory to prevent this rare but disastrous complication of gemcitabine therapy.

Adenocarcinoma↗
PubMed1999

The low molecular weight apo(a) phenotype is an independent predictor for coronary artery disease in hemodialysis patients: a prospective follow-up.

Patients with end-stage renal disease treated by hemodialysis have a tremendous risk for cardiovascular complications that cannot be explained by traditional atherosclerosis risk factors. Lipoprotein(a) (Lp(a)), a risk factor for these complications in the general population, is significantly elevated in these patients. In this study, it was determined whether Lp(a) and/or the genetically determined apo(a) phenotype are risk predictors for the development of coronary artery disease in these patients. A cohort of 440 unselected hemodialysis patients were followed for a period of 5 yr independent of the cause of renal disease, duration of preceding treatment, and the preexistence of coronary artery disease at study entry. Coronary events defined as definite myocardial infarction, percutaneous transluminal coronary angioplasty, aortocoronary bypass, or a stenosis >50% in the coronary angiography were the main outcome measure. Sixty-six (15%) of the 440 patients suffered a coronary event during follow-up. In univariate analysis, patients with events were significantly older and showed a trend to lower HDL cholesterol concentrations, and higher apolipoprotein B and Lp(a) concentrations without reaching significance. Apo(a) phenotypes of low molecular weight, however, were significantly more frequent in patients with compared to those without events (43.9% versus 21.9%, P<0.001). The other lipids, lipoproteins, and apolipoproteins were similar in both groups. Multiple Cox proportional hazards regression analysis found age and the apo(a) phenotype to be the best predictors for coronary events during the observation period, independent of whether patients with a preexisting coronary artery disease or an age >65 yr at the study entry or both were excluded from the analysis. Diabetes mellitus was a risk factor only in presence of a low molecular weight apo(a) phenotype. The genetically determined apo(a) phenotype is a strong and independent predictor for coronary events in hemodialysis patients. Apo(a) phenotyping might be helpful to identify hemodialysis patients at high risk for coronary artery disease.

Adult↗