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Direct oral anticoagulants (DOACs) are among the most commonly prescribed medications, and DOAC-associated kidney dysfunction may be a problem that is underrecognized by clinicians. We report on the case of an 82-year-old patient who, two weeks after the prescription of rivaroxaban for atrial fibrillation, was hospitalized for a drug-induced hypersensitivity syndrome whose main clinical manifestations were low-grade fever with a petechial rash in the legs and acute renal failure (ARF). Within one week after rivaroxaban withdrawal, the patient’s clinical condition improved and the renal function normalized. In a review of the literature, we only found five case reports of rivaroxaban-related ARF: two patients had tubulo-interstitial nephritis (TIN), two had anticoagulant-related nephropathy (ARN), and the last one had IgA nephropathy. As some recent publications suggest that kidney injury due to anticoagulation drugs may be largely underdiagnosed, we also analyzed the data from the VigiAccess database, the World Health Organization pharmacovigilance program that collects drug-related adverse events from 134 national registries worldwide. Among all the rivaroxaban-associated adverse events reported in VigiAccess since 2006, 4,323 (3.5%) were renal side effects, of which 2,351 (54.3%) were due to unspecified ARF, 363 (8.4%) were due to renal hemorrhage (characteristically associated with ARN), and 24 (0.6%) were due to TIN. We also compared these results with those reported in VigiAccess for other DOACs and vitamin K antagonists. This analysis suggests that the frequency of renal adverse events associated with rivaroxaban and other DOACs may be appreciably higher than what one might currently consider based only on the small number of fully published cases.

Cardiology guidelines recommend measuring high-sensitivity cardiac troponin (hs-cTn) for the diagnostic work-up of acute coronary syndromes (ACS). Many hospitals measure hs-cTnT, but preliminary data have shown that hs-cTnT is higher than normal in many hemodialysis patients without evidence of ACS. The purpose of this study was therefore to determine the hs-cTnT levels every month for 1 year in asymptomatic hemodialysis patients, in order to assess their changes over time relative to creatine kinase.Fourty-four hemodialysis patients (mean age 67 ± 14 years) were included. The predialysis levels of fifth-generation hs-cTnT, CK, and CK-MB were measured every month for 1 year using a Cobas® 6000 analyzer (Roche Diagnostics, Switzerland).Almost 100% of hs-cTnT measurements were higher than normal (N 14 ng/L); the mean ± SD annual level was 84 ± 59 ng/L, ranging from a minimum of 24 ± 2 to 241 ± 28 ng/L in individual patients. The mean levels of CK and CK-MB were normal. Thirteen myocardial infarctions were analyzed, which were all associated with an initial elevation in hs-cTnT45% from the individual baseline value. By comparison, CK and CK-MB only increased in 38% and 31% of these myocardial infarctions, respectively.hs-cTnT is persistently higher than normal in chronic hemodialysis patients. Standard algorithms for diagnosing ACS can obviously not be used and alternative diagnostic strategies need to be developed. According to our data, and given the huge variation in baseline hs-cTnT levels among patients, the use of higher cut-offs as proposed in the literature cannot be recommended. Instead, we consider that hs-cTnT should be checked at regular intervals (e.g., every 3-6 months) in order to establish individual baseline levels for hs-cTnT. This approach, in most instances, not only makes it possible to more rapidly rule-in but also to rapidly rule-out, cases of ACS in hemodialysis patients who develop cardiac symptoms.

Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers. Vancomycin, cefazolin, and aminoglycosides have historically been regarded as the primary intravenous antimicrobials administered with IHD given their relatively low cost, convenient dosing, and longevity of clinical use. Despite this, a growing body of literature is evaluating the use of an expanded list of antimicrobials that may be employed using post-dialysis dosing for patients requiring IHD; however, the available data are largely limited to pharmacokinetic studies and small cohorts of infected patients or uninfected subjects. Post-dialytic dosing of intravenous antimicrobials may be considered on a patient-by-patient basis after careful consideration of clinical, microbiological, and logistical factors that may influence the probability of treatment success. This document reviews and evaluates currently available information on the post-dialytic administration of an expanded list of intravenous antimicrobials in the setting of thrice-weekly, high-flux IHD.

Ureteral stenosis is a rare manifestation of granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis). We report the case of a 76-year-old woman with progressive renal failure in which bilateral hydronephrosis due to ureteral stenosis was the first manifestation of the disease. Our patient also had renal involvement with pauci-immune crescentic glomerulonephritis associated with high titers of anti-proteinase 3 c-ANCAs, but no involvement of the upper or lower respiratory tract. The hydronephrosis and renal function rapidly improved under immunosuppressive therapy with high-dose corticosteroids and intravenous pulse cyclophosphamide. We reviewed the literature and found only ten other reported cases of granulomatosis with polyangiitis/Wegener’s granulomatosis and intrinsic ureteral stenosis: in two cases, the presenting clinical manifestation was unilateral hydronephrosis and in only two others was the hydronephrosis bilateral, but this complication developed during a relapse of the disease. This case emphasizes the importance of including ANCA-related vasculitis in the differential diagnosis of unusual cases of unilateral or bilateral ureteral stenosis.

Background In hemodialysis patients, post-dialysis treatment with intravenous antibiotics permits even severe infections to be managed on an outpatient basis. Cefepime is a fourth-generation cephalosporin with a broad spectrum of action in monotherapy. We report on the pharmacokinetics of cefepime in post-dialysis therapy. Methods Since June 2012, twelve infections were treated with post-dialysis cefepime in 9 patients on high-flux hemodialysis. The initial post-dialysis dose of cefepime was approximately 15 mg/kg. The following doses were adapted according to the trough serum levels obtained before the subsequent dialysis in order to be above the EUCAST breakpoints for susceptible organisms and above the MIC90. Residual plasma concentrations were determined before (n = 30) and after (n = 17) dialysis by liquid chromatography–mass spectrometry. Results Overall, the mean ± SD dose of cefepime was 920 ± 270 mg (14.5 ± 5.1 mg/kg), but it was significantly lower before the 48 h interval (775 ± 210 mg or 12.7 ± 4.5 mg/kg) compared to the 72 h interval (1125 ± 225 mg or 17.2 ± 4.9 mg/kg) (p 1 mg/l) with the exception of Pseudomonas aeruginosa (>8 mg/l). Cefepime concentrations were higher in anuric patients compared to those with preserved diuresis (15.6 ± 3.5 vs 9.25 ± 3.6 mg/l; p

Contrast-induced acute kidney injury (CI-AKI) classically occurs following the intravascular administration of iodinated contrast medium (CM). However, some cases of iodine-induced nephrotoxicity have been reported in patients who did not receive intravascular CM, as a consequence of iodine absorption through mucosae, burned skin or interstitial tissues. Recently, we observed the first case of CI-AKI occurring after an enteroclysis without any direct intravascular injection of CM. Here, we report this case, and review other clinical situations in which renal toxicity has been reported following the non-intravascular use of iodinated compounds.

The aim of the present study was to evaluate the dose of postdialysis cholecalciferol needed to maintain the 25-hydroxyvitamin D [25(OH)D] levels in the optimal range of 75–150 nmol/L. Twenty-six patients who had low baseline 25(OH)D levels (mean27.5±14.9 nmol/L) were studied. The 25(OH)D levels were measured every 2 months for one year. During the first two months, all the patients received 2000 IU of cholecalciferol after each hemodialysis (=6000 IU/wk). Thereafter, the dose was individualized and adapted every 2 months by administering 1 to 6 cholecalciferol tablets (2000 IU each) per week (total weekly dose = 2000–12000 IU/wk). During cholecalciferol supplementation, the 25(OH)D concentrations rapidly increased from baseline to140.1±28.3 nmol/L at month 6 and95.6±20.9 nmol/L at month 12. At month twelve, 86% of the patients had 25(OH)D levels within the target range with a mean dose of5917±4106 IU/wk of cholecalciferol; however, the amount needed to maintain these levels varied widely from 0 (n=2) to 12000 IU/wk (n=5). In conclusion, postdialysis cholecalciferol prescription is quite effective in correcting vitamin D deficiency/insufficiency, but the amount of cholecalciferol needed to maintain the 25(OH)D levels within the optimal range over the long-term varies widely among patients and must be individualized.

BACKGROUND: Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9 micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5 +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by approximately 2.5% (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients without OVD there was a significant reduction of approximately 34% (from 32.7+/-14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were reduced by > 15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P = 0.001). CONCLUSIONS: These results indicate that the homocysteine-lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.

We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.

QUESTIONS UNDER STUDY Diagnosis of acute kidney injury (AKI) relies on measurement of serum creatinine (SCr). SCr is a late marker of impaired renal function. Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) has given encouraging results for an early and sensitive detection of AKI. This cohort study was conducted (1) to assess the value of uNGAL as early marker of contrast-induced AKI (CI-AKI) in unselected patients undergoing percutaneous coronary procedure (PCP) and (2) to investigate whether uNGAL levels correlate with the volume of contrast medium (CM) used during the procedure. METHODS We enrolled 244 consecutive adult patients undergoing PCP done with the low-osmolar CM Iomeprolum (median volume of CM 122 [88-168] ml per procedure). uNGAL was measured at its peak with a standardised clinical laboratory platform (ARCHITECT uNGAL assay, Abbott). RESULTS Overall, the post-PCP uNGAL levels were extremely low in our cohort with a median value of 7.7 [4.0-14.5] ng/ml (N ≤132 ng/ml). Twenty-five (10%) patients developed CI-AKI according to the classical diagnostic criteria (≥25% or ≥44.2 µmol/l increase in SCr) and 8 (3.3%) patients according to the AKIN criteria. Regardless of the definition considered, uNGAL levels did not significantly differ in patients with or without CI-AKI. Similarly, we found no significant correlation between the volume of CM used and the post-PCP uNGAL levels (r = -0.11). CONCLUSIONS In a large cohort of unselected adult patients, uNGAL measured four to six hours after PCP was ineffective to predict the risk of CI-AKI and did not correlate with the volume of CM used during the procedure.

Contrast-induced nephropathy (CIN) is an acute renal injury due to the renal toxicity of iodinated contrast media. It is classically defined as a relative (≥25%) or absolute (≥0.5 mg/dl; 44 μmol/l) increase in serum creatinine from baseline value. CIN accounts for 10 to 15% of hospital-acquired acute renal failure and may rarely lead to irreversible renal function loss. Following percutaneous coronary intervention, reported incidence of CIN varies between 0 to more than 20%, depending on the prevalence of risk factors and used definition. Nowadays, the diagnosis of CIN relays on serum creatinine monitoring, although it is a late marker of acute kidney injury. Given the expanding number of percutaneous coronary interventions made in outpatient settings and the morbidity and mortality associated with CIN, early detection of CIN is of utmost clinical relevance. Several plasmatic and urinary biomarkers have been studied in that view, with plasmatic cystatine-C and urinary NGAL being the most promising. As no treatment specifically targets CIN once it develops, the main goal for clinicians remains prevention, with hydration status optimisation being the only proven strategy to date. Here, we will review the recent evidence concerning CIN, its incidence, proposed early diagnostic biomarkers, as well as its treatment and prognostic implication.

Urea kinetic modeling: An in vitro and in vivo comparative study. The urea kinetic model (UK) and the direct dialysis quantification method based on dialysate collection (DDQ) were used to determine the urea distribution volume (V) identified with the total body water and the urea generation rate (G) for different dialysis times, both in vivo during short hemodialysis (N = 20) and in vitro using an experimental single-pool urea system (N = 10). Both UK and DDQ allowed a satisfactory in vitro estimation of V and G for all dialysis times. On the other hand in vivo V and G estimations by both methods showed an increase of more than 50% between the determinations performed after 30 minutes of dialysis and at the end of dialysis. Our theoretical analysis shows that the in vivo changes of V are compatible with those expected for a two-compartment system in which one compartment is cleared faster than the other. Furthermore, given that urea is allowed to equilibrate in the body at the end of dialysis, DDQ permits an accurate estimate of V, G and PCR even for short hemodialysis, which UK does not.

Background. The prevalence and significance of higher than normal cardiac troponin I (cTnI) levels in asymptomatic chronic hemodialysis (HD) patients remains a source of discussion. The aim of the present study was to evaluate the prevalence of higher than normal cTnI levels in asymptomatic HD patients, as determined by the last generation of immunoassay, and to perform further cardiological investigations in those patients with persistently elevated cTnI levels. Methods. All chronic HD patients in our center who had exhibited no symptoms of coronary artery disease (CAD) during the previous four weeks were screened. cTnI levels were determined before dialysis in all patients using the last generation AccuTnI™ assay (UniCel DxI 800, Beckman Coulter). The cTnI levels of those patients with elevated cTnI at the screening evaluation were then measured monthly for six months. We were thus able to identify a group of patients with persistently elevated cTnI levels (> 3 consecutive months) who subsequently underwent cardiac echography and dipyridamole-exercise (D-E) thallium testing. If stress myocardial ischemia was detected, a coronary angiography was then performed. Results. Fifty patients (32 males) were included: mean age 62.8 ± 13.6 years, 20 (40%) with a history of CAD, and 21 (42%) diabetic. At the initial screening, the mean cTnI concentration was 0.05 ± 0.06 μg/L and the cTnI levels were higher than normal (> 0.09 μg/L) in six patients (12%). In the follow-up, the cTnI normalized immediately in two patients but remained persistently elevated (range, 0.10–0.48 μg/L) in four (8%). These four patients (all males, one diabetic) had a mean age of 70.2 ± 6.6 years, and all had heart failure with a history of severe CAD with previous myocardial infarction (n = 4), coronary stenting (n = 3), and/or bypass (n = 2). D-E thallium imaging showed reversible myocardial ischemia in all. The stress ischemia involved one to four cardiac segments and was slight to moderate in three patients and severe in the diabetic patient. A coronary angiogram was performed in all patients, and showed lesions of variable severity: severe three-vessel CAD with severe systolic dysfunction in two patients (including the diabetic), and non-critical/ peripheral coronary stenosis in the other two. Conclusions. Among the asymptomatic HD patients in our center, we identified four (8%) with persistently elevated cTnI levels, as determined using the last generation AccuTnI™ assay. All of them had a history of severe CAD with heart failure and exhibited reversible myocardial ischemia upon D-E thallium imaging; coronary angiography revealed coronary lesions of variable severity. Overall, our data indicate that persistent low-grade cTnI elevation occurs in HD patients having longstanding severe cardiac disease, but, from our data, it is difficult to reach a conclusion as to the best clinical approach for this group of patients.

We report the case of a 62-year-old man without prodromal symptoms who developed a hemolytic-uremic syndrome (HUS) one week after the diagnosis of an acute bacteremic urinary infection (UTI). In this patient, the E. coli isolated in blood cultures was a non-O157:H7 Shigatoxin-producing strain that could subsequently be identified as O138:H-. This is a strain that is normally found in pigs and that has never been isolated in humans previously. UTI-related HUS is a rare event, as until now, only 14 pediatric and 3 adult cases have been reported. Indeed, this new case, besides its interesting microbiological aspects, should heighten our awareness of UTI-related HUS as a rare but real condition, not only in young children but also in adult patients. This should emphasize the necessity to search actively for other sources of Shigatoxin-producing E. coli in patients presenting with HUS without gastrointestinal symptoms.

Calciphylaxis, also called calcific uraemic arteriolopathy, is a rare disease characterized by medial calcification of the small arteries and ischaemia of the subcutaneous tissue, often leading to necrosis of subcutaneous fat and skin. It affects mainly women with chronic renal insufficiency and/or obesity. According to recent studies, calciphylaxis seems to occur more frequently than previously believed, with an incidence of 1% per year [1] and a prevalence of 4% in dialysis patients [2]. The pathogenesis of calciphylaxis is poorly understood and its treatment is largely empirical and somewhat controversial. Recent studies have emphasized the crucial role of a multidisciplinary therapeutic approach focusing on the correction of the underlying abnormalities of the calcium and phosphorus plasma concentrations (using non-calcium-containing phosphate binders), local wound care with debridement of necrotic tissues and aggressive treatment of infectious complications [3]. The utility of parathyroidectomy, corticoid therapy and hyperbaric oxygen therapy remains controversial. However, despite intensive combined treatments, the prognosis of calciphylaxis remains poor: the overall 1 year survival is 45% and the 5 year survival is 35%, with a relative risk of death of 8.5 compared with other dialysis patients [4]. Bisphosphonates have a powerful inhibitory effect on osteoclast activity and bone resorption and are largely used in the treatment of osteoporosis, tumoral hypercalcaemia and Paget’s disease. Some previous studies have shown that bisphosphonates also have beneficial effects on the evolution of experimental calciphylaxis [5,6] and tumoral calcinosis with systemic inflammatory response [7]. According to these latter observations, we decided to treat a woman with chronic renal failure and rapidly worsening calciphylaxis with pamidronate. This treatment brought a spectacular and rapid improvement of the patient’s clinical condition and a rapid decrease of the inflammatory syndrome. We report this case, which is, to our knowledge, the first one in which a bisphosphonate has been used to treat a patient with calciphylaxis.

We report the case of a 78-year-old hypertensive diabetic patient without evidence of renal artery stenosis who had moderate chronic renal insufficiency, which had been stable for several years under low-dose captopril therapy, and who rapidly developed acute renal failure when irbesartan was prescribed. Unfortunately the medication was not stopped promptly and the patient never recovered his basal renal function and had to undergo chronic hemodialysis. This observation emphasizes the importance of a careful monitoring of renal function in patients receiving angiotensin II receptor antagonists.

We retrospectively studied the prevalence, histologic features, clinical correlations, and long-term outcome of the intrarenal vascular lesions of lupus nephritis (LN) in a series of 169 renal biopsies performed between 1980 and 1994 in 132 patients with systemic lupus erythematosus. The most common vascular lesions were nonspecific sclerotic changes, found in 37% of the biopsies (24% if only the cases with moderate to severe changes are considered). The other common vascular lesions were "immunoglobulin microvascular casts," found in 24% of the biopsies. Vasculitis and thrombotic microangiopathy were rare lesions and were seen in only 4 (2.4%) and 1 (0.6%) cases, respectively. Isolated sclerotic vascular changes were present in biopsies from older patients with a longer duration of LN, compared with the group with no vascular lesions, and were associated with a significantly higher prevalence of hypertension. Overall, however, the long-term renal and patient survival of this group did not differ significantly from that of the patients without vascular changes. Immunoglobulin microvascular casts (IMCs) ("lupus vasculopathy") were characterized by the presence of immunoglobulin deposition within the glomerular capillaries and small arterioles. In the present study we extensively investigated the morphologic and immunologic features of this lesion. The lesions were notable for the absence of endothelial or parietal vascular lesions and of fibrin, platelets, and leukocytes, which indicates that thrombosis is not involved in the vascular obstruction. According to our data immunoglobulin precipitation in the microvasculature seems to play a central role in the pathogenesis of this lesion, which is why we propose the term "immunoglobulin microvascular casts." In general, IMCs were associated with the most severe and active forms of diffuse proliferative lupus nephritis (World Health Organization [WHO] class IV). However our data show that, in contrast to previous studies, the long-term outcome of patients with IMCs is not worse than that of other patients with class IV LN. It may even be somewhat better, suggesting that this type of lesion may reverse with immunosuppressive therapy. In addition, we did not find any association between the presence of IMCs and the lupus anticoagulant, IgG anticardiolipin antibodies, or extrarenal vascular manifestations. Concerning vasculitis and thrombotic microangiopathy, our results confirm that their occurrence is quite rare in-lupus nephritis. The outcome of our 4 patients with vasculitis was not particularly poor, which could be related to early and/or aggressive treatment. Taken as a whole, our data confirm that the presence of active and severe forms of diffuse proliferative LN (WHO class IV) carries a worse prognosis compared with the other forms of LN. In our study, and in agreement with previous reports (23), the long-term renal survival of patients with class IV LN was significantly worse than that of patients with other forms of LN, with a 10-year renal survival of 70% compared with 85%, respectively. However our data do not support the conclusions of some previous studies that the presence of intrarenal vascular lesions is a marker of poor renal prognosis in lupus nephritis. More precisely, our data show that the somewhat poorer renal outcome observed in patients with IMCs is related to the fact that in most cases these lesions are associated with class IV lupus nephritis, and not related to the presence of the vascular lesion per se.

Water soluble vitamins in chronic hemodialysis patients and need for supplementation. Forty-three patients on chronic hemodialysis who before the present study had only received a low-dose supplement of folic and ascorbic acid were studied prospectively for one year. After baseline values were obtained in month one, increasing doses of postdialysis vitamin supplements were prescribed for the vitamins which were found to be insufficient in order to determine the minimal amount of oral postdialysis supplement necessary to normalize vitamin levels. According to our results no systematic supplement was indicated for biotin, riboflavin or vitamin B12. For folic acid and vitamin C, supplementation with lower doses than those prescribed in many dialysis units allowed optimal vitamin levels in the majority of patients; 2 to 3 mg/week (300 to 400 µg/day) of folic acid and of 1000 to 1500 mg/week (150 to 200 mg/day) of vitamin C was considered sufficient. A severe pyridoxine deficiency was present in most (> 80%) unsupplemented patients, either as judged by pyridoxal-5-phosphate determinations in plasma or determination of specific enzyme activation in erythrocytes (EGOTo and α-EGOT); a postdialysis supplement of at least 100 to 150 mg/week of pyridoxine hydrochloride (> 15 to 20 mg/day) corrects this deficiency. The activity of the thiamine-dependent enzyme transketolase in erythrocytes (ETKo) was insufficient in 35% and marginal in 21% of the patients, while whole blood thiamine determined simultaneously in 10 of the ETKo-deficient patients was within the normal range. These results suggest that in uremia insufficient transketolase activity may be related to inhibition of the enzymatic system rather than to true vitamin deficiency. On a long-term basis a supplement of 200 to 300 mg/week of thiamine hydrochloride (30 to 45 mg/day) restored ETKo to satisfactory levels in most patients; whether this supplement is to be recommended warrants further studies.

To the Editor: There is little doubt that coronary calcification is associated with cardiovascular mortality.