Human papillomaviruses (HPV) are epitheliotropic viruses, with some types suggested to be associated with skin cancer. In this study, swab samples collected from five different sites on the skin of renal transplant recipients, dialysis patients, and age-and sex-matched healthy controls were analyzed for HPV DNA by a newly designed PCR test. Most individuals were found to have asymptomatic HPV infections; more specifically, 94% of the renal transplant patients, 82% of the dialysis patients, and 80% of the healthy controls were positive for HPV DNA. The multiplicity of the HPVs detected was astounding: 20 previously described and 30 putatively new types were identified by cloning and sequencing of 33 samples from 13 individuals. These results demonstrate that normal human skin harbors an array of papillomaviruses, most of them previously unknown.To date, 85 different genotypes of the human papillomaviruses (HPV) have been fully characterized. In addition to being the causative agents of common skin warts, there is evidence that certain types of HPV play a role in the pathogenesis of skin cancer associated with the rare hereditary disease epidermodysplasia verruciformis (EV) (22, 27), and they are therefore designated EV-associated HPV.Renal transplant recipients given immunosuppressive therapy for long periods of time have an increased incidence of cutaneous neoplasia (2,10,29). Also, more than 90% of kidney recipients develop skin warts and 40% develop skin cancer within 15 years of transplantation, a 50-to 100-fold increase compared to the general population (7), and EV-associated HPV types have been found in skin tumors from such patients (5,12,16,21,28). Interestingly, EV HPV types have also been detected in hairs plucked from normal skin of 94% of renal transplant recipients (8) and 67% of healthy controls (9), and in another study (1), 35% of biopsy specimens of normal skin obtained during cosmetic surgery were positive for HPV DNA.In a recent report (20), we presented a PCR test that holds promise as a potent tool for exploring HPV both in skin tumors and in normal skin. In the present investigation, we used the test to study the presence of HPV at various sites on normal skin of both renal patients who were or were not on immunosuppression and matched healthy controls, and there is a serendipitous aspect to the results. MATERIALS AND METHODSSubjects. We studied 52 of about 130 renal transplant recipients being followed up at the outpatient clinic of nephrology of Malmö University Hospital, Malmö, Sweden. The median time since transplantation was 5 years and 2 months, and the range was 2 months to 26 years. Also included in the study were 28 of the 67 patients being treated at the Dialysis Unit; the median length of dialysis treatment was 2 years and 5 months (range, 1 month to 14 years). All of the transplant and dialysis patients were randomly selected, and a sex-and age-matched healthy control was recruited for each of the patients. The age range of the individuals in the three groups was 21 to 80 years,...

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Background: Serum creatinine is the most commonly used marker for estimation of glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR marker, several prediction equations including several parameters are being used, with the Modification of Diet in Renal Disease (MDRD), Schwartz, and CounahanBarratt equations being the ones most widely accepted for estimation of relative GFR in mL ⅐ min ؊1 ⅐ (1.73 m 2 ) ؊1 . The present study analyzes whether these GFR prediction equations for adults and children might be replaced by simple prediction equations based on plasma concentrations of cystatin C. Methods: Data from 536 patients (0.3-93 years), consecutively referred for determination of GFR by an invasive gold standard procedure, were used for the analysis. Calculations of bias (median percentage of error), correlation (adjusted R 2 ), and percentage of estimates within 30% and 50% of measured GFR were used in the comparisons. Results: A cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor:

While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

Comparisons with the CKD-EPI and MDRD equations suggest that the LM equations are superior for the present Swedish population, due to markedly higher accuracy of the LM equations at measured GFR <30 mL/min/1.73 m(2). However, the LM equations cannot be recommended for use in general clinical practice until validated in other populations.

A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.

OBJECTIVETo study trough levels of metformin in serum and its intra-individual variation in patients using a newly developed assay.RESEARCH DESIGN AND METHODSTrough serum levels of metformin were measured once using liquid chromatography–tandem mass spectrometry (LCMSMS) in 137 type 2 diabetic patients with varying renal function (99 men) and followed repeatedly during 2 months in 20 patients (16 men) with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 body surface.RESULTSPatients with eGFR >60, 30–60, and <30 ml/min/1.73 m2 had median trough metformin concentrations of 4.5 μmol/l (range 0.1–20.7, n = 107), 7.71 μmol/l (0.12–15.15, n = 21), and 8.88 μmol/l (5.99–18.60, n = 9), respectively. The median intra-individual overall coefficient of variation was 29.4% (range 9.8–74.2).CONCLUSIONSDetermination of serum metformin with the LCMSMS technique is useful in patients on metformin treatment. Few patients had values >20 μmol/l. Metformin measurement is less suitable for dose titration.

t In 1976, Cockcroft and Gault introduced a widely used formula comprising several anthropometric variables to compensate for the inadequacies of creatinine level as a marker of glomerular filtration rate (GFR). The present work investigates the possibility of introducing cystatin C-based formulas without anthropometric variables to predict GFR, determined by an invasive "gold standard" procedure (iohexol clearance), and to compare the diagnostic efficiency of such formulas with that of Cockcroft and Gault. All 451 adult patients referred to the University Hospital for determination of GFR by iohexol clearance measurements during a period of 6 months were included in the study. Calculations of bias (median percent error), correlation (adjusted R2), and accuracy (percentage of estimates within 30 and 50% of iohexol clearance) were used in the comparison. The cystatin C-based formula GFR (ml/min)=89.12 x cystatin C(-1.675) had lower bias and higher accuracy in predicting GFR than the Cockcroft-Gault formula. If a cystatin C-based formula including gender was constructed: GFR (ml/min)=99.19 x cystatin C(-1.713) x (0.823 for women), an even lower bias and higher accuracy were obtained. It is suggested that measurement of cystatin C should be used for the initial prediction of GFR of a patient.