Clinical Kidney Journal - current issue

Atypical anti-glomerular basement membrane disease: lessons learned

Glassock, R. J. — 2016-09-26T10:20:42-07:00

Anti-glomerular basement membrane (GBM) disease usually pursues a self-limited course, at least from the immunological perspective. In addition, circulating antibodies to cryptic, conformational epitopes within the NC1 domain of the alpha 3 chain of Type IV Collagen are commonly found at the zenith of the clinical disease. However, exceptions to these general rules do occur, as exemplified by two remarkable cases reported in this issue of the Clinical Kidney Journal. The possible explanations for and the lessons learned from these uncommon occurrences are discussed in this short commentary.

Multiple recurrences of anti-glomerular basement membrane disease with variable antibody detection: can the laboratory be trusted?

Liu, P., Waheed, S., Boujelbane, L., Maursetter, L. J. — 2016-09-26T10:20:42-07:00

Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occurrence, symptoms resolved with plasmapheresis, intravenous methylprednisone and oral cyclophosphamide. The relationship between anti-GBM antibody findings and disease presentation is complex. Clinicians should be aware of the possibility of seronegative anti-GBM disease.

Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time

Gu, B., Magil, A. B., Barbour, S. J. — 2016-09-26T10:20:42-07:00

Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody–positive flares with pulmonary and renal involvement, and anti-GBM antibody–negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over time. Disease severity paralleled the detection of anti-GBM antibodies but was independent of IgG subtype staining along the GBM. This case suggests a role for changing subpopulations of pathogenic antibodies as an explanation for variation in disease phenotype and anti-GBM antibody results.

FGF23 in kidney transplant: the strange case of Doctor Jekyll and Mister Hyde

Cianciolo, G., Cozzolino, M. — 2016-09-26T10:20:42-07:00

During the last decade, a new view into the molecular mechanisms of chronic kidney disease-mineral bone disorder (CKD-MBD) has been proposed, with fibroblast growth factor 23 (FGF23) as a novel player in the field. Enhanced serum FGF23 levels cause a reduction in serum phosphate, together with calcitriol suppression and consequent hyperparathyroidism (HPT). In contrast, reduced serum FGF23 levels are associated with hyperphosphatemia, higher calcitriol levels and parathyroid hormone (PTH) suppression. In addition, serum FGF23 levels are greatly increased and positively correlated with serum phosphate levels in CKD patients. In this population, high serum FGF23 concentration seems to predict the occurrence of refractory secondary HPT and to be associated with higher mortality risk in incident haemodialysis patients. In living-donor kidney transplant recipients, a faster normalization of FGF23 and phosphate levels with a lower prevalence of HPT, may be considered a major pathway to investigate.

FGF23 is associated with early post-transplant hypophosphataemia and normalizes faster than iPTH in living donor renal transplant recipients: a longitudinal follow-up study

2016-09-26T10:20:43-07:00

Background

We aimed to longitudinally analyse changes in the levels of serum fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH) and associated minerals in patients undergoing renal transplantation.

Methods

Sixty-three patients with end-stage renal disease (ESRD) who underwent living donor transplantation were recruited. Serum FGF23, iPTH, uric acid, inorganic phosphorous (iP), blood urea nitrogen and serum creatinine were measured pre-transplant and at 1 (M1), 3 (M3) and 12 months (M12) post-transplantation.

Results

FGF23 levels were decreased at M1, M3 and M12 by 93.81, 96.74 and 97.53%, respectively. iPTH levels were decreased by 67.95, 74.95 and 84.9%, respectively. The prevalence of hyperparathyroidism at M1, M3 and M12 post-transplantation was 63.5, 42.9 and 11.1%, respectively. FGF23 and iP levels remained above the normal range in 23 (36.5%) and 17 (27%) patients at M1, 10 (15.9%) and 5 (8%) at M3 and in none at M12 post-transplantation, respectively. A multivariate regression model revealed that, pre-transplant, iP was positively associated with iPTH (P = 0.016) but not with FGF 23; however, post-transplant, iP level was negatively associated with FGF23 (P < 0.001) but not with iPTH.

Conclusions

Post-transplant FGF23 levels settle faster than those of iPTH. However, 11% of patients continued to have hyperparathyroidism even after 12 months.

Serum FGF23 levels may not be associated with serum phosphate and 1,25-dihydroxyvitamin D levels in patients with Fanconi syndrome-induced hypophosphatemia

Goto, S., Fujii, H., Kono, K., Watanabe, K., Nakai, K., Nishi, S. — 2016-09-26T10:20:43-07:00

Fibroblast growth factor 23 (FGF23) is regulated by sustained phosphate supplementation and restriction. However, few studies have investigated FGF23 levels in patients with Fanconi syndrome. Therefore, we evaluated intact and C-terminal FGF23 and FGF23-associated parameters in four patients with Fanconi syndrome. Serum intact and C-terminal FGF23 levels were extremely low. Although serum phosphate and 1,25-dihydroxyvitamin D levels improved to or above the normal range within 1 year of treatment with oral phosphate and calcitriol, serum FGF23 levels remained low. Serum FGF23 levels in patients with Fanconi syndrome might be regulated by novel factors other than serum phosphate and 1,25-dihydroxyvitamin D levels.

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

2016-09-26T10:20:43-07:00

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.

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: Why to measure glomerular filtration rate with iohexol?

2016-09-26T10:20:43-07:00

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.

Cardiovascular-renal complications and the possible role of plasminogen activator inhibitor: a review

D'Elia, J. A., Bayliss, G., Gleason, R. E., Weinrauch, L. A. — 2016-09-26T10:20:43-07:00

Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin–angiotensin–aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction. While the renin–angiotensin–aldosterone system and growth factors, such as transforming growth factor-beta (TGF-β), are almost always part of the process, there are rare experimental observations of PAI-1 expression without their interaction. Here we review the literature on PAI-1 and its role in vascular, fibrotic and oxidative injury as well as work suggesting potential areas of intervention in the pathogenesis of multiple disorders.

Approach to atherosclerotic renovascular disease: 2016

Daloul, R., Morrison, A. R. — 2016-09-26T10:20:43-07:00

The management of atherosclerotic renal artery stenosis in patients with hypertension or impaired renal function remains a clinical dilemma. The current general consensus, supported by the results of the Angioplasty and Stenting for Renal Atherosclerotic Lesions and Cardiovascular Outcomes for Renal Artery Lesions trials, argues strongly against endovascular intervention in favor of optimal medical management. We discuss the limitations and implications of the contemporary clinical trials and present our approach and formulate clear recommendations to help with the management of patients with atherosclerotic narrowing of the renal artery.

Comparison of trends in colorectal cancer screening in the US end-stage renal disease population and the US Medicare population

Fwu, C.-W., Kimmel, P. L., Eggers, P. W., Abbott, K. C. — 2016-09-26T10:20:43-07:00

Background

Although patients treated with maintenance hemodialysis are at an increased risk of colorectal cancer compared with the general population, national practices for colorectal cancer screening have not been reported in this population. We assessed the performance of colorectal cancer screening in the US end-stage renal disease program in comparison with the US Medicare population.

Methods

We studied the United States Renal Data System for US prevalent hemodialysis patients between 2002 and 2011 who had Medicare as their primary insurer. We assessed procedure codes for performance of common colorectal cancer screening tests, including fecal occult blood testing, sigmoidoscopy and colonoscopy. We assessed screening sigmoidoscopy and screening colonoscopy only and excluded patients who had preexisting colon cancer or gastrointestinal hemorrhage. Because colorectal cancer screening recommendations are established for hemodialysis patients who have been listed for kidney transplantation, but no general recommendations exist for patients who are not wait-listed, we assessed colorectal cancer screening separately for the two groups.

Results

We found that 1-year performance of colonoscopy in wait-listed hemodialysis patients was similar to or higher than that in general Medicare patients of the same age, while performance of colonoscopy in non-wait-listed patients was significantly lower than among general Medicare patients of the same age.

Conclusions

Given improved survival among hemodialysis patients in the last decade, the utility of colorectal cancer screening even among non-wait-listed hemodialysis patients should be reassessed.

The impact of haemodialysis arteriovenous fistula on haemodynamic parameters of the cardiovascular system

2016-09-26T10:20:43-07:00

Background

Satisfactory vascular access flow (Qa) of an arteriovenous fistula (AVF) is necessary for haemodialysis (HD) adequacy. The aim of the present study was to further our understanding of haemodynamic modifications of the cardiovascular system of HD patients associated with an AVF. The main objective was to calculate using real data in what way an AVF influences the load of the left ventricle (LLV).

Methods

All HD patients treated in our dialysis unit and bearing an AVF were enrolled into the present observational cross-sectional study. Fifty-six patients bore a lower arm AVF and 30 an upper arm AVF. Qa and cardiac output (CO) were measured by means of the ultrasound dilution Transonic Hemodialysis Monitor HD02. Mean arterial pressure (MAP) was calculated; total peripheral vascular resistance (TPVR) was calculated as MAP/CO; resistance of AVF (AR) and systemic vascular resistance (SVR) are connected in parallel and were respectively calculated as AR = MAP/Qa and SVR = MAP/(CO – Qa). LLV was calculated on the principle of a simple physical model: LLV (watt) = TPVR·CO². The latter was computationally divided into the part spent to run Qa through the AVF (LLV_AVF) and that part ensuring the flow (CO – Qa) through the vascular system. The data from the 86 AVFs were analysed by categorizing them into lower and upper arm AVFs.

Results

Mean Qa, CO, MAP, TPVR, LLV and LLV_AVF of the 86 AVFs were, respectively, 1.3 (0.6 SD) L/min, 6.3 (1.3) L/min, 92.7 (13.9) mmHg, 14.9 (3.9) mmHg·min/L, 1.3 (0.6) watt and 19.7 (3.1)% of LLV. A statistically significant increase of Qa, CO, LLV and LLV_AVF and a statistically significant decrease of TPVR, AR and SVR of upper arm AVFs compared with lower arm AVFs was shown. A third-order polynomial regression model best fitted the relationship between Qa and LLV for the entire cohort (R² = 0.546; P < 0.0001) and for both lower (R² = 0.181; P < 0.01) and upper arm AVFs (R² = 0.663; P < 0.0001). LLV_AVF calculated as % of LLV rose with increasing Qa according to a quadratic polynomial regression model, but only in lower arm AVFs. On the contrary, no statistically significant relationship was found between the two parameters in upper arm AVFs, even if mean LLV_AVF was statistically significantly higher in upper arm AVFs (P < 0.0001).

Conclusions

Our observational cross-sectional study describes statistically significant haemodynamic modifications of the CV system associated to an AVF. Moreover, a quadratic polynomial regression model best fits the relationship between LLV_AVF and Qa, but only in lower arm AVFs.

Cutaneous Mycobacterium chelonae infection distal to the arteriovenous fistula

2016-09-26T10:20:43-07:00

A few single cases of Mycobacterium chelonae skin infection have been reported in haemodialysis patients. We report three additional cases that share peculiar clinical characteristics, pointing to diagnostic clues. All three cases presented as erythematous nodules developing distally to a proximal arteriovenous fistula (AVF). This presentation was identical to that of two published cases. A survey of all Belgian haemodialysis units during the period 2007–11 yields an estimated incidence of ~0.9/10 000 patient-years. Although the source of M. chelonae remains unclear, this specific clinical presentation should be added to the listing of potential complications of an AVF and should be recognized, as it is fully treatable if diagnosed by culture and tissue biopsy.

FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease

2016-09-26T10:20:43-07:00

Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R² = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients.

RENEW--a renal redesign project in predialysis patient care

Sau Fan Chow, J., Jobburn, K., Chapman, M., Suranyi, M. — 2016-09-26T10:20:43-07:00

Background

An ageing population and geographical growth, along with an increase in the number of people that reside in specific location, are increasing the demand for renal replacement therapies. Hospital-based haemodialysis units are struggling to cope with the associated physical, staffing and cost demands. Home-based dialysis therapies are known to be more cost effective with superior social, physical health and survival outcomes.

Methods

‘RENEW, a renal redesign project, examined the pre-dialysis health care experience of renal patients to find opportunities to improve patient care outcomes and increase the uptake of home-based dialysis therapies. This article details two crucial parts of the approach to change management: (i) diagnostics—an inclusive, client focused, multidisciplinary approach to identify issues relating to the pre-dialysis journey—and (ii) solution design—an inclusive problem-solving approach to identify and marry solutions to the issues identified during diagnostics.

Results

Based on feedback from patients/caregivers and staff interviews, utilizing a clinical redesign methodology, a new model of care was developed, implemented and subsequently embedded into clinical practice. The results have been evident via improved care coordination, enhanced patient preparation for dialysis, improved patient psychosocial welfare and, importantly, an increased number of patients planned for and commencing home dialysis. This has empowered patients by giving them the confidence, knowledge and skills to be actively engaged in their own care. The project resulted in significant expenditure avoidance.

Conclusion

Change management strategies with successful implementation are vital components of evolving clinical practice to achieve both clinical and organizational goals.

Applying effective teaching and learning techniques to nephrology education

Rondon-Berrios, H., Johnston, J. R. — 2016-09-26T10:20:43-07:00

The interest in nephrology as a career has declined over the last several years. Some of the reasons cited for this decline include the complexity of the specialty, poor mentoring and inadequate teaching of nephrology from medical school through residency. The purpose of this article is to introduce the reader to advances in the science of adult learning, illustrate best teaching practices in medical education that can be extrapolated to nephrology and introduce the basic teaching methods that can be used on the wards, in clinics and in the classroom.

Announcements

2016-09-26T10:20:43-07:00