BMC Nephrology - Latest Comments

Correction

Randy Carter — 2012-01-04T11:41:41Z

The horizontal axis in Figure 2, and in Figure 3, is the beta-weighted sum of Z-scores (i.e., the linear predictor minus its intercept) not the linear predictor (lp) as stated in the legend. In Figure 2, for example, the probability of HCH is plotted versus lp+1.21; not versus lp.

A clinical trial is required before stopping the use aluminium as a phosphate binder.

sandawana william majoni — 2011-09-12T13:47:35Z

Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice?
This is a very important question which warrants a rigorous debate and a well conducted clinical trial. Depending on where one is practising nephrology, aluminium is still being used as a phosphate binder but very carefully, if at all, because of the history which has been clearly elucidated in this review article. Aluminium is an important, powerful and well tolerated phosphate binder, the use of which should be revisited since the previous association with very serious complications due to accumulation are now very rare with the use of treated water for dialysis. At present with the available evidence which is comprehensively discussed in this article, it is difficult to easily prescribe this binder but at the same time the evidence is not there to completely discard it on the basis of the current evidence for toxicity. It is very important not to completely discard this without proper evidence. Historically, the are examples of drugs which were discarded on the basis of severe and serious adverse effects but are coming back into clinical practice after careful clinical studies for safety and efficacy and these include thalidomide which is now commonly used for treatment of myeloma and other conditions.
The authors practice should be commented for the courage they have shown in continuing to use the binder, albeit with careful monitoring, realising the potential for side effects and at the same time realising its potential for saving lives of dialysis patients. All the current accepted binders have issues. Patients complain that calcium based binders are not palatable despite the various attempts to flavour them. This leads to a number not adhering to the prescribed phosphate binding. This is in addition to the accumulating evidence of exacerbation of vascular calcification; the prevention of which the phosphate binding and bone mineral disorder control is aimed at in the first place. Savelamer has got the same problem with size of tablets being a major issue for some patients and, as mentioned by the authors, available evidence is not strong enough to warrantee using it as the sole binder for lack of outcome data, the high cost and the fact that it is a relatively new binder despite the positive evidence for possible cardiovascular risk reduction. Lanthanum is a new binder, which is still quite expensive and with little experience and no current clinical outcomes data. The available evidence as discussed by the authors point to lack of the best binder and aluminium may well be that binder.
As the authors have alluded to, a properly conducted clinical trial comparing currently used ‘safe ‘binders should be carried out and it is feasible for this to be done. This should not just be a clinical trial for proving the safety or otherwise of aluminium as a binder but as mentioned, there is clear evidence that some of the binders we currently use may not be as safe as originally thought and the newer binders are not yet tested. Hard Outcome data is not very robust with the newer binders as well and this will need to be tested.
Recently, results of several clinical trials in nephrology have proved that it is not only possible to do large scale clinical trials in nephrology but also that the results may prove that the commonly held views may not be accurate[1-4].
I therefore agree with the authors that the careful use of aluminium is warranted and that a large scale clinical trial will be needed before we can dismiss its use based on a history which may not be related to its use as a phosphate binder at all.

1. Baigent, C., et al., The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet, 2011. 377(9784): p. 2181-92.
2. Cooper, B.A., et al., A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis. New England Journal of Medicine, 2010. 363(7): p. 609-619.
3. Pfeffer, M.A., et al., A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease. New England Journal of Medicine, 2009. 361(21): p. 2019-2032.
4. Drüeke, T.B., et al., Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia. New England Journal of Medicine, 2006. 355(20): p. 2071-2084.

Life span of permcath

vinu thomas — 2009-09-23T09:54:25Z

Does ethanol locking affect the longevity of double lumen catheters?. In the article it is mentioned that upto 2 weeks of alcohol exposure does not harm the catheter.suppose we plan to retain a catheter for 6 months or even one year, what will be the impact?

Comparing For-Profit and Not-for-Profit Dialysis Facilities

Philip Zager — 2008-12-10T12:46:01Z

We read with interest the recent article entitled “Comparative mortality of hemodialysis patients at for-profit and not-for-profit dialysis facilities in the United States, 1998 to 2003: A retrospective analysis” by Foley et al. Many of these authors have major roles in assembling the United States Renal Data System’s (USRDS) Annual Data Report (ADR). The 2007 ADR states “[standardized mortality and hospitalization ratios] remain lowest in Dialysis Clinic Inc. (DCI) units, with no other providers showing the same consistency in results.” DaVita (DV), Fresenius Medical Care of North America (FMCNA) and DCI are, by far, the largest for-profit and not-for-profit facilities, respectively, operating in the United States. According to the USRDS the standardized mortality (SMRs) and hospitalization ratios (SHRs) have been lower in DCI than in DaVita and FMCNA each year from 1999 to 2006. The published SMRs adjusted for age, gender, race, primary diagnosis and ESRD vintage during 1999, 2003 and 2006 respectively are for DCI - 0.859, 0.796, 0.898; for DV- 0.865, 0.872, 0.992 and for FMCNA- 0.896, 0.934, 1.005. Similarly, adjusted SHRs published for the same years for DCI are 0.878, 0.861, 0.891; for DV- 0.975, 0.969, 1.025 and for FMCNA- 0.967, 0.982, 1.133. Therefore, the conclusion of this article that there are no significant differences in mortality among hemodialysis patients treated in for-profit and not-for-profit facilities is surprising. These apparently conflicting results bring to light the inherent challenges associated with SMRs and SHRs and Cox regression analysis to compare clinical outcomes between different providers.

There are several factors that may have contributed to the discordant results published in the USRDS ADR and the current manuscript. First, there are important methodological differences between the calculations of SMRs, SHRs versus the use of Cox regression models, including the larger number of covariates which may be included in the latter. The unadjusted Cox models reported in this article showed significantly lower mortality among patients treated in not-for-profit facilities. Nevertheless, we agree that adjustment for case mix is warranted. However, virtually all of the co-morbid conditions were either similarly distributed or more prevalent among patients treated by not-for-profit providers. Second, the inclusion of hospital days as a covariate, while a potentially useful surrogate marker of comorbidity, may be problematic. If, not-for-profit facilities provide care in a manner that leads to fewer hospitalizations, adjusting hospitalization may be inappropriate since it may be a causal pathway through which not-for-profit providers achieve lower mortality. Third, the study population in the present study was not restricted to DV, FMCNA and DCI, but rather included 100% ESRD sample from the Medicare database to select patients who were first dialyzed between January 1, 1998, and December 31, 2003; had Medicare as primary payer throughout the exposure period; and were on hemodialysis at either a for-profit or not-for-profit dialysis facility at the end of the exposure period. Therefore, the differences in outcomes between DV, FMCNA versus DCI may have been diluted out by the inclusion of additional patients.

It is challenging to assess clinical outcomes in a rapidly evolving environment. Given the competitive economic pressures, it is highly unlikely that a prospective randomized study will ever be undertaken to compare outcomes among patients treated in for-profit versus not-for profit facilities. Therefore, it is necessary to develop novel statistical techniques to better assess outcomes from administrative databases.

For the authors: Christopher Adams, MD1

Karen S. Servilla, MD1,2

Dana Miskulin, MD3

Philip Zager, MD1,2,4

1University of New Mexico Health Sciences Center, Department of Internal Medicine, Division of Nephrology, Albuquerque, NM

2 Nephrology Section, New Mexico Veterans Affairs Health Care System, Albuquerque, NM, Albuquerque, NM

3 Tufts New England Medical Center, Boston, MA

4 Dialysis Clinic, Inc. Quality Management Division, Albuquerque, NM

Additional information regarding author's contributions

Adrian Mondry — 2005-02-01T06:02:38Z

Zhu Ai Ling has contributed significantly to writing the drafts on which the original manuscript submitted in July 2004 is based. As such, her contribution should be acknowledged as follows:

"A.-L. Z. did statistical analysis and contributed considerably to the drafting of the original manuscript. As such, she should be considered joined first author together with A.M. and M.N."

Response to COMMENT: MEFV mutations and renal pathology

Patrick Fisher — 2004-01-05T01:00:51Z

I would like to thank Konstantopoulos, et al. for their interest in our paper and their respective comments. Furthermore, I would like to respond to the comments made by Konstantopoulos regarding our paper entitled:

Familial Mediterranean fever, Inflammation and Nephrotic Syndrome: Fibrillary Glomerulopathy and the M680I Missense Mutation [1].

A. The clinical diagnosis in our patient was made based on the highly recognized Tel-Hashomer criteria [2], which was the same criteria used by Tunca,et al. in the article which was referenced by Konstantopoulos [3]. Furthermore, no evidence was provided by Konstantopoulos to support the comment that "resistance to colchicine treatment ...can make [the] diagnosis [of] [FMF] doubtful". Again the reference which was cited [3], does not support their aforementioned statement.

B. Regarding the comment on the genetic analysis utilized in identifying the MEFV genotype in our patient:

Our paper clearly states that only nine mutations were tested for out of more than 40 mutations identified to-date. We obviously agree that this test, performed at the time by the UCLA Medical Center in Los Angeles, CA USA,"cannot exclude additional mutation(s) of the MEFV gene".

C. Regarding the comment that "detection of a single mutation in people of Armenian ancestry does not per se support FMF diagnosis strongly":

In our patient, only one out of nine mutations tested for was detected. However,the diagnosis of FMF in our patient is strongly supported by the Tel-Hashomer criteria [2], irrespective of the genotype. Futhermore, we cannot be certain that this patient has another missense mutation that has since been identified and which he was not originally tested for. [1]

References

1. Fisher PW, Ho LT, Goldschmidt R, Semerdjian RJ & Rutecki GW. Familial Mediterranean fever, Inflammation and Nephrotic Syndrome: Fibrillary Glomerulopathy and the M680I Missense Mutation. BMC Nephrol. 2003 Aug 11;4(1):6.

2. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M: Criteria for the diagnosis of familial Mediterranean fever.

Arthritis Rheum 1997, 40:1879-1885.

3. Tunca M, Tankurt E, Akbaylar Akpinar H, Akar S, Hizli N & Gonen O.The efficacy of interferon alpha on colchicine-resistant familial Mediterranean fever attacks: a pilot study. Br J Rheumatol. 1997, 36:1005-1008.

MEFV mutations and renal pathology

Kostas Konstantopoulos — 2003-11-27T21:16:18Z

We like to comment on the work by Fisher et al on glomerulopathy complicating a case of clinical Familial Mediterranean Fever (FMF) carrying also a single MEFV mutation [1].

A. Although the clinical diagnosis of FMF sounds clear, the final resistance to colchicine treatment in the certain patient, observed in 25% of all true cases [2] can make diagnosis doubtful.

B. Mutation screening according to the method applied by the authors is limited to the few mutations tested for [3]. This method does not exclude additional mutation(s) of the MEFV gene.

C. The MEFV mutation frequency in Armenians may approximate 1:5; therefore, detection of a single mutation in people of Armenian ancestry does not per se support FMF diagnosis strongly.

D. We have in the past published two cases of the so-called phenotype II of FMF (renal amyloidosis as a presenting symptom in homozygotes). Interestingly, the one case carried M694V/V726A and the other carried the M680I/M694V mutations [4,5]. Although in our cases no indication for a glomerulopathy was evident, in the one of them, diagnosis was based on histochemical detection of amyloid A component only, the Congo red staining being negative and renal size being normal. Therefore, an un-detectable by light microscopy glomerular pathology cannot be excluded. On the other hand, one should not ignore that glomerulonephritis, parenchymous nephritis and lipoid nephrosis occur with an increased frequency in FMF and their inter-relation and relation with amyloidosis remains a classical dispute [6]

It seems that the biological effects of MEFV mutations as far as renal pathology is concerned needs further clarification in various categories of patients. This effect must also be considered in the context of the prevalence of these mutations in several populations.

Kostas Konstantopoulos (kkonstan@med.uoa.gr)

Alexandra Kanta

Department of Medicine I, Athens University Medical School, Athens-11527 Greece

References

2. Tunca M, Tankurt E, Akbaylar Akpinar H, Akar S, Hizli N & Gonen O.The efficacy of interferon alpha on colchicine-resistant familial Mediterranean fever attacks: a pilot study. Br J Rheumatol. 1997, 36:1005-1008

3. Eisenberg S, Aksentijevich I, Deng Z, Kastner DL, Matzner Y. Diagnosis of familial Mediterranean fever by a molecular genetics method. Ann Intern Med. 1998, 129(7):539-542.

4. Konstantopoulos K, Michael S, Kanta A, Pecheux C, Grateau J, Helioti H & Stathakis C. Renal amyloidosis as a first manifestation of Familial Mediterranean Fever. Scand J Rheumatol. 2000, 29:129-130

5. Konstantopoulos K, Kanta A, Tzoulianos M, Dimou S, Sotsiou F, Politou M & Loukopoulos D. Familial Mediterranean fever phenotype II in Greece. Isr Med Assoc J. 2001, 3:862-863.

6. Heller H, Sohar E, Gafni J & Heller J. Amyloidosis in familial mediterranean fever. An independent genetically determined characteristic. Arch Intern Med 1961, 107: 539-590