letter to the editor
outcome of ESRD. NNT should be used with caution in
nonsignificant results.2 In a non-significant NNT, a hazard
ratio could hypothetically also be a negative number, which
would then constitute a number needed to harm.3 This is not
clinically meaningful. Thus, the reader is advised to not be
swayed by the better NNT of nonsignificant outcomes in this
article, but rather concentrate on the question of clinical
utility of NNT of 410 in the overall study population
(Po0.05) to prevent one ESRD over 5 years.
1. Perkovic V, Heerspink HL, Chalmers J et al. Intensive glucose control
improves kidney outcomes in patients with type-2 diabetes. Kidney Int
2013; 83: 517–523.
2. Eric Corty. Using And Interpreting Statistics: A Practical Text for the Health,
Behavioral, and Social Sciences. Mosby, 2007.
3. Muthu. V. The number needed to treat: problems describing
non-significant results. Evid Based Mental Health 2003; 6: 72.
Jyoti E. Brar1
1
Department of Nephrology, SUNY Buffalo, Buffalo, New York, USA
Correspondence: Jyoti E. Brar, Department of Nephrology, SUNY Buffalo,
11th Floor, 462 Grider Street, Buffalo, New York 14226, USA.
E-mail: jyotieknoorbrar@yahoo.com
Kidney International (2013) 84, 621–622; doi:10.1038/ki.2013.239
The Authors Reply: We agree with the cautious approach
advocated by Dr Brar in interpreting number needed to
treat values when the 95% confidence interval for the
hazard ratio straddles unity.1 However, it is important to
consider how to most appropriately generalize trial results
from one population to either a broader population or, as in
this case, a more narrowly defined subpopulation. This is
particularly important to the prevention of kidney failure,
where most of the risk during the relatively short period
of a randomized trial (compared with the usual time course
of progressive diabetic nephropathy) is observed in the
population that already has evidence of kidney disease at
baseline.
In our post hoc analysis of the ADVANCE trial results, we
have attempted to address this by conducting further
subgroup analyses by baseline kidney function (Figure 3).
The appropriate method of comparing subgroup results is to
check whether the results of the subgroups are consistent
with each other, using both a qualitative assessment
and a formal test for statistical heterogeneity. The results of
this analysis are clear in ADVANCE: consistent efficacy
(hazard ratios of 0.2 compared to 0.4) and no evidence
of heterogeneity (P heterogeneity ¼ 0.54). Whether or not
individual subgroups attain statistical significance is not key,
given that the power is, inevitably, limited in subgroup
analyses. It also does not make sense to ignore the different
absolute effect sizes potentially achievable in different
subpopulations, where specific data regarding efficacy are
not available. For example, this sort of criterion would
make contemporary risk-based cardiovascular prevention
impossible, as trials specifically conducted in people at high
622
risk have not been conducted, but are instead inferred from
trials conducted in broader populations.
1. Brar JE. Caution advised in interpreting non-significant results from
ADVANCE post hoc analysis. Kidney Int 2013; 84: 621–622.
Vlado Perkovic1, Mark Woodward1,
Sophia Zoungas2 and John Chalmers1
1
George Institute for Global Health, Sydney, New South Wales, Australia and
2
School of Public Health and Preventative Medicine, Monash University,
Melbourne, Victoria, Australia
Correspondence: Vlado Perkovic, George Institute for Global Health, PO Box
M201, Missenden Road, Sydney, New South Wales 2050, Australia,
E-mail: vperkovic@thegeorgeinstitute.org
Kidney International (2013) 84, 622; doi:10.1038/ki.2013.241
Comments on ‘KDIGO 2012 clinical
practice guideline for the
evaluation and management of
chronic kidney disease’
To the Editor: ‘KDIGO 2012 Clinical Practice Guideline for
the Evaluation and Management of Chronic Kidney Disease’1
fills a gap, now including very recent and new insights into
the diagnosis and therapy of chronic renal disease. The
structured presentation emphasizes this in various chapters
coherently, including pediatric considerations. It is to be
expected that these guidelines will represent the future basis
for quick information on chronic kidney disease and not only
for nephrologists. As happens in such an extensive overview,
some well-known but older observations may have been lost
owing to the quantity of new data, and in my opinion some
statements are painfully missed for the diagnosis and
treatment of chronic kidney disease.
One objection concerns the diagnosis of suspected
myeloma (Chapter 1, p. 62), which is incomplete. There is
no reference to the sulfosalicylic acid test as a rapid, helpful
and cheap (!) screening method in those cases in which the
reagent strip test (stick test) does not react or shows only
minor degrees of proteinuria.2,3 Another conflicting issue is
in Chapter 4, Table 32, p. 103. In the section ‘antimicrobials’,
penicillins might be better replaced by b-lactam antibiotics
because penicillins belong to the greater group of b-lactam
antibiotics to which the cephalosporins also belong. They are
more frequently used in clinical practice, and neurotoxicity
is also observed during treatment with these compounds.4
Furthermore, the side effects of b-lactam antibiotics should
be broadened by the addition of the term ‘bleeding disorders’.
Benzylpenicillin in high doses (10–40 Mio IU ¼ 6–24 g/day) is
used for the treatment of invasive group B streptococci5 in
patients in whom renal function is frequently compromised
by septicemia, necrotizing fasciitis, or glomerulonephritis. If
no dosage adjustment is undertaken, severe bleeding may
appear owing to platelet dysfunction6 (besides the well-
known neurotoxic properties). In contrast to benzylpenicillin,
Kidney International (2013) 84, 621–625

other b-lactam antibiotics, i.e., some cephalosporins, might
cause a hypoprothrombinemia in patients with renal failure
and low vitamin K levels (malnutrition, parenteral feeding) by
interfering with vitamin K metabolism if there is no dosage
reduction.7 In Chapter 4, p.104 ‘Evidence Base’, the reference
to patients with myeloma among the risk factors for AKI
following radiocontrast media is lacking.8 As the authors8
stated, it ‘would seem prudent to avoid the use of contrast
agents in patients with plasma cell dyscrasie’.
1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.
KDIGO 2012 clinical practice guideline for the evaluation and management
of chronic kidney disease. Kidney Int Suppl 2013; 3: 1–150.
2. Davison AM, Grünfeld JP. History and clinical examination of the patient
with renal disease. In: Cameron S, Davison AM, Grünfeld JP et al. (eds)
Oxford Textbook of Clinical Nephrology. Vol. 1. Oxford University Press:
Oxford, 1992; pp 1–15.
3. Hinberg IH, Katz L, Waddell L. Sensitivity of in vitro diagnostic dipstick test
to urinary protein. Clin Biochem 1978; 11: 62–64.
4. Grill MF, Maganti R. Cephalosporin-induced neurotoxicity: clinical mani-
festations, potential pathogenic mechanisms, and the role of electro-
encephalographic monitoring. Ann Pharmacother 2008; 42: 1843–1850.
5. Sendi P, Johansson L, Norrby-Teglund A. Invasive group B streptococcal
disease in non-pregnant adults. Infection 2008; 36: 100–111.
6. Sattler FR, Weitekamp MR, Ballard FR. Potential for bleeding with new
beta-lactam antibiotics. Ann Int Med 1986; 105: 924–931.
7. Shearer MJ, Bechtold H, Andrassy K et al. Mechanism of cephalosporin-
induced hypoprothombinemia: relation to cephalosporin side chain,
vitamin K metabolism, and vitamin K status. J Pharmacol 1988; 28: 88–95.
8. Berns AS. Nephrotoxicity of contrast media. Kidney Int 1989; 36: 730–740.
Konrad M. Andrassy1
1
University Hospital, Ruprecht-Karls University of Heidelberg, Heidelberg,
Germany
Correspondence: Konrad M. Andrassy, University Hospital, Ruprecht-Karls
University of Heidelberg, Im Neuenheimer Feld 162, D-69120 Heidelberg,
Germany. E-mail: mt8@ix.urz.uni-heidelberg.de
Kidney International (2013) 84, 622–623; doi:10.1038/ki.2013.243
The Authors Reply: On behalf of the workgroup and
KDIGO leadership, we thank Dr Andrassy for his review of
the guideline, and comments.1 The guidelines are intended to
help the reader appreciate the complexity of the subject,
distill key clinical points, and inform future research and
clinical care. They are not intended as textbooks of medicine,
nor do they replace the need for formal study or review of
specific topics by clinicians.
We had specifically stated in the preamble and in other
overviews that this guideline does not replace formal texts,
and would not cover details of work-up for specific diag-
noses, nor would it address all treatments in detail. Thus,
while appreciating the comments made by Dr Andrassy, we
do not believe that these omissions are deleterious to the
overall guideline. In fact, the comments help to remind us
of the value of text books and other resources, and the
complementary value of guidelines. These are all tools to help
clinicians and others.
1. Andrassy KM. Comments on ‘KDIGO 2012 clinical practice guideline for the
evaluation and management of chronic kidney disease’. Kidney Int 2013;
84: 622–623.
Kidney International (2013) 84, 621–625
letter to the editor
Adeera Levin1 and Paul E. Stevens2
1
Division of Nephrology, University of British Columbia, Vancouver, Canada
and 2Kent Kidney Care Centre, East Kent Hospitals University, NHS
Foundation Trust, Canterbury, UK
Correspondence: Adeera Levin, Division of Nephrology, University of British
Columbia, 1081 Burrard Street, Room 6010A, Vancouver, British Columbia,
Canada V6Z1Y8. E-mail: alevin@providencehealth.bc.ca
Kidney International (2013) 84, 623; doi:10.1038/ki.2013.244
The hidden secret of acute kidney
injury: the urologist!
To the Editor: We would like to congratulate Li et al.1 on
their contribution to the report on World Kidney Day
(WKD) 2013, focusing on acute kidney injury (AKI),
published in the Journal.
In our experience, there is often another hidden cause that
must be taken into account: urologists treating renal colic
(and not kidney stones!).
According to the European Association of Urology
Guidelines,2 pain relief is the first therapeutic step in
patients with acute stone episodes: nonsteroidal anti-
inflammatory drugs (NSAIDs) are the first-choice medical
treatment.
Accordingly, urologists can conservatively treat patients
with renal colic due to a small distal stone expected to pass
spontaneously, by taking the easy step of prescribing NSAIDs.
However, in our experience, 25% of patients with renal colic
treated with NSAIDs suffered AKI, and in all cases these were
patients with recurrent pain.
Considering that our emergency department sees more
than 1000 patients a year because of pain due to ureteric
stones,3 the number of cases with AKI secondary to the use of
NSAIDs for recurrent renal colic is marked.
The patients in question are often not old, but young,
without multiple comorbidities or infections.
Our experience of renal colic confirms the need to stress
this information also to urologists, perhaps adding a specific
alert comment to the Guidelines noting the risks of AKI in
case of recurrent renal colic treated conservatively, so that
select cases can be switched early to invasive treatment.
Sometimes apparently ‘quick-and-easy’ medical treatment
can cause a severe medical problem.
DISCLOSURE
We declare that this communication has not been published and is
not under consideration for publication elsewhere. We declare that
all material in this assignment is our own work and does not involve
plagiarism. The authors declared no competing interests.
1. Li PK, Burdmann EA, Mehta RL. Acute kidney injury: a global health alert.
Kidney Int 2013; 83: 372–376.
2. Türk C, Knoll T, Petrik A et al. EAU Guidelines on urolithiasis. 2012; http://
www.uroweb.org/gls/pdf/20_Urolithiasis_LR%20March%2013%202012.pdf.
3. Dal Moro F, Abate A, Lanckriet GR et al. A novel approach for accurate
prediction of spontaneous passage of ureteral stones: support vector
machines. Kidney Int 2006; 69: 157–160.
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