Given a broad topic like ‘Clinical Nephrology,’ one might think that a guest editor would be obliged to fill the table of contents with material that represents the full spectrum of our ever-more-diverse and complex field. Instead, in attempting to discern a theme in the resulting contents, I see that I have assembled a more limited set of topics that reflects, inevitably, some of my personal interests. Perhaps the entire collection fits under the rubric of ‘Chronic Kidney Disease’ (CKD), which after all, is probably the major clinical focus for most practicing nephrologists. We all have access to textbooks and reviews, but those are not usually where one finds ‘Current Opinions.’ My own preferences tend towards reading the current opinions of smart and well informed people about controversies in their fields of study.
Do all patients with kidney stones have CKD? My own answer is ‘of course they do.’ (Conflict of interest disclosure: I am a calcium oxalate stone former, so it is not pleasing to answer affirmatively.) Kidney stone doctors want to make the case that lithology is under-represented in the world's universities and medical centers. This is particularly surprising in light of the continued increase in kidney stone prevalence in the United States and elsewhere. Many academic nephrology centers do not have a nephrologist specializing in, or researching, evaluation and management of stone formers. One would think this an attractive field: stone specialists see younger and healthier patients than most of us see in our dialysis units, although recent data make clear that such patients have a surprisingly higher rate of progression to end stage kidney disease and a higher overall mortality than their nonstone forming matched controls . Those facts make clear that stone patients have a chronic kidney disease ‘with implications for health’, as the KDIGO definition of CKD requires .
Three articles in this edition of Current Opinion in Nephrology and Hypertension highlight topics that constitute common postlecture questions on the topic of kidney stones. First, is potassium citrate indicated in the treatment of calcium phosphate stones? It is possible that I have never given a lecture on stone disease without being asked this question. Calcium phosphate stones are far less frequent than calcium oxalate stones. The controversy arises because citrate is well known to effectively reduce calcium crystallization so that supplementation with potassium citrate is a common prescription to reduce stone recurrence. However, citrate metabolism by the liver consumes protons, essentially generating bicarbonate, and causing urinary alkalinization. The resultant increase in urine pH increases the calculated (by EQUIL2) supersaturation of calcium phosphate. In the absence of randomized trials of citrate supplementation for calcium phosphate, the clinical consequence is uncertain: does the inhibitory effect of citrate on calcium crystallization supervene over the crystal promoting effect of higher urine pH? Dr Jeffrey Rimer of University of Houston, and Drs Khashayar Sakhaee and Naim Maalouf of University of Texas Southwestern, review the topic thoroughly .
A second question kidney stone lecturers are asked is whether kidney stone formers can be kidney donors to transplant recipients. We have been struck by the heterogeneity of transplant programs’ answers to this question. We are sometimes asked for consultation by well intended stone formers who have been rejected by the transplant program of their first-degree relative. Dr Vasishta Tatapudi, transplant nephrologist at New York University Langone Health, and I review the varied American and international guidelines, and demonstrate that the guidelines are becoming more liberal in their willingness to accept stone-forming donors . Long-term follow-up of such donors is really lacking.
Whatever the topic in stone disease, further research of these matters requires standardization of the answers offered to a third question: what is a stone recurrence? Reading the literature and designing clinical trials reveal that definitions of that term are varied and as heterogeneous as definitions of ‘progression of CKD.’ Dr Andrew Rule and Dr Matthew D’Acosta of the Mayo Clinic, with Dr Vernon Pais of Dartmouth, review the extant terminology and propose how clinical research should proceed .
The other topics presented here are similarly controversial, with our esteemed authors opining about clinical questions that arise frequently. The theme of three articles regards safety of our prescriptions. What is the role of gadolinium in MRI of patients with CKD? We may have all thought that this controversy was resolved and ‘nephrogenic’ systemic fibrosis was not going to be diagnosed again. Instead, we are being asked to do hemodialysis following administration of gadolinium-based contrast agents, as radiologists have been falsely reassured that a greater number of CKD patients can now safely receive them. Dr Brent Wagner and Ms Katarina Leyba of the University of New Mexico take a less reassuring point of view and highlight the lack of long-term data .
Are nonsteroidal anti-inflammatory drugs dangerous in CKD? If so, are nephrologists contributing to the daily toll of the opioid epidemic by prescribing opiates to patients with CKD, or are they not treating pain effectively at all? The absolute prohibition of NSAIDs for CKD patients may be unnecessary and ill-advised, according to Dr Sriram Sriperumbuduri and Dr Swapnil Hiremath of the University of Ottawa .
Should angiotensin-converting enzyme inhibitors and angiotensin receptor blockers be stopped if CKD progresses? Should they be prescribed for patients who are first seen with more advanced stages of CKD? Nephrologists are understandably famous for their proclivity to prescribe these classes of drugs, which acutely lower glomerular filtration rate with the expectation that there will be a long-term benefit. These difficult and vexing questions are addressed by Dr Roopa Shah and Dr Matt Sparks of Duke University .
What is the role of sex in affecting the care and health of patients with CKD? The answers provided by Dr Amarpali Brar and Dr Mariana Markell of the State University of New York Downstate Medical Center delineate both differences in the biology of men and women, and also indicate that providers probably contribute to some disturbing and interesting disparities . The conclusion is that greater attention needs to be directed at understanding the relevant variables.
Finally, Ms. Margaret Armstrong and Dr Christie Thomas of the University of Iowa reply to the question of how genetics will play a role in the diagnosis of causes of CKD. A frustrating aspect of the care of patients is the high proportion who progress without a specific cause diagnosed. Patients may present late, and kidney biopsies demonstrate nonspecific findings. The improving availability and continually falling prices of more widely applicable genetic testing is likely to replace kidney biopsy in an increasing number of cases .
There is a broad spectrum of categories of nephrologic disorders that are not covered in this slim edition of ‘Clinical Nephrology.’ But I am confident that this edition of Current Opinions in Nephrology and Hypertension does offer opinions that address some of the popular and frequently discussed controversies.
I appreciate the help of Brian Ward, Editorial Coordinator, in assembling this edition.
Financial support and sponsorship
The author appreciates the support of The Rare Kidney Stone Consortium (RKSC), part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), the National Center for Advancing Translational Sciences (NCATS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The consortium is funded through collaboration between NCATS and the NIDDK (U54DK083908-01).
Conflicts of interest
I have served as a consultant for Allena, Alnylam and Retrophin; I have received honoraria for lectures from Retrophin; I am a patent holder for, and owner of, the Ravine Group.
1. Dhondup T, Kittanamongkolchai W, Vaughan LE, et al. Risk of ESRD and mortality in kidney and bladder stone formers. Am J Kidney Dis 2018; 72:790–797.
2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work GroupKDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3:1–150.
3. Rimer JD, Sakhaee K, Maalouf NM. Citrate therapy for calcium phosphate stones. Curr Opin Nephrol Hypertens 2019; 28:130–139.
4. Tatapudi VS, Goldfarb DS. Differences in national and international guidelines regarding use of kidney stone formers as living kidney donors. Curr Opin Nephrol Hypertens 2019; 28:140–147.
5. D’Costa MR, Pais VM, Rule AD. Leave no stone unturned: defining recurrence in kidney stone formers. Curr Opin Nephrol Hypertens 2019; 28:148–153.
6. Leyba K, Wagner B. Gadolinium-based contrast agents: why nephrologists need to be concerned. Curr Opin Nephrol Hypertens 2019; 28:154–162.
7. Sriperumbuduri S, Hiremath S. The case for cautious consumption: NSAIDs in chronic kidney disease. Curr Opin Nephrol Hypertens 2019; 28:163–170.
8. Shah R, Sparks MA. Renin–angiotensin system inhibition in advanced chronic kidney disease: how low can the kidney function go? Curr Opin Nephrol Hypertens 2019; 28:171–177.
9. Brar A, Markell M. Impact of gender and gender disparities in patients with kidney disease. Curr Opin Nephrol Hypertens 2019; 28:178–182.
10. Armstrong ME, Thomas CP. Diagnosis of monogenic chronic kidney diseases. Curr Opin Nephrol Hypertens 2019; 28:183–194.