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• Author's reply to Taylor
  Hassib Narchi
  Published on: 9 January 2022
• Risk of hypertension in children with multicystic dysplastic kidney
  C Mark Taylor
  Published on: 9 January 2022

• Published on: 9 January 2022

  Author's reply to Taylor

  • Hassib Narchi, Consultant paediatrician

  Dear Editor,

  We can reassure Taylor that the wider context of hypertension associated with multicystic dysplastic kidney (MCDK) was not missed in this review, for the following reasons:

  1. The purpose of the review was to quantify the risk of hypertension associated with a unilateral MCDK based on longitudinal cohort studies, irrespective of the mechanism(s) for that hypertension, and which single case re...

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  Dear Editor,

  We can reassure Taylor that the wider context of hypertension associated with multicystic dysplastic kidney (MCDK) was not missed in this review, for the following reasons:

  1. The purpose of the review was to quantify the risk of hypertension associated with a unilateral MCDK based on longitudinal cohort studies, irrespective of the mechanism(s) for that hypertension, and which single case reports definitely cannot answer. We are therefore confident that all cases, regardless of their theoretical pathophysiology for hypertension, have been included. Interestingly, the case reports cited by Taylor seem to invalidate his statement that the absence of renal elements in the non- functioning MCDK makes it unlikely to be the cause of hypertension, as most showed that nephrectomy of the dysplastic kidney led to normalisation of the blood pressure. These simple clinical observations highlight how much we do not know despite the numerous theories and animal experiments extensively referenced by Taylor.

  2. Taylor correctly reminds us that abnormalities in the controlateral kidney probably increase the risk of hypertension. This is exactly why, in an attempt to quantify the risk of a single affected kidney, only unilateral MCKD with a radiologically normal controlateral kidney were analysised. The number of nephrons in the radiologically normal controlateral kidney was obviously not available in any of the cohort studies, nor is it currently routinely sought when following up such children. It remains therefore impossible to validate if Taylor's statement of the number of nephrons in the controlateral kidney applies to all children with unilateral MCDK. Again, this does not matter at all in our review as we included all hypertensive children regardless of the possible mechanism for hypertension.

  3. We also mentioned that many cases of unilateral renal agenesis (RA) may be due to involution of a MCDK. However, as it is impossible retrospectively to correctly attribute each case of RA to that involution process, we felt it was inappropriate to include all cases of RA to those with unilateral MCDK. The theoretical effect of reduction of the number of nephrons in unilateral RA on the risk of hypertension is certainly important, but unilateral RA was specifically excluded in this review.

  4. Taylor rightly questions the dichotomous studied outcome: hypertension versus normal blood pressure. Unfortunately, this was how the studied cohorts classified the outcomes, and, in the absence of specific blood pressure measurements given for each child, that was the only information available for analysis.

  5. The study of 24-hour blood pressure monitoring mentioned by Taylor was specifically excluded as it dealt with children with a solitary kidney, who were excluded for the many reasons given above. In addition, 24-hour blood pressure monitoring was not available in all the selected cohorts. We also stated that longer follow up studies are required.

  6. Taylor also implies that there is already information on that outcome. Unfortunately, it takes more than case reports and experimental animal data to provide a quantitative answer to the family of a child with MCDK : "doctor, what is the risk of my child having hypertension later in life?", and this regardless of the possible different mechanisms underlying their hypertension. This review, despite its limitations, provides an estimate, albeit imperfect, of that risk, and more importantly, shows the methods required to develop much needed better prospective longitudinal studies, based on a national MCDK registry and using stricter blood pressure measurements reporting over a much longer period, as discussed also in the preceding 2 paragraphs.

  7. We agree that BP monitoring in adulthood is required, but not only for these children, but also for the whole population where the risk of hypertension of any cause is already very high. However this recommendation, although important, still does little to provide an answer today to the question asked by the family of a child with MCDK. Fortunately, the systematic review, despite its many weaknesses, brings today the answer a little bit closer.

  Hassib Narchi

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  Conflict of Interest:
  None declared.

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• Published on: 9 January 2022

  Risk of hypertension in children with multicystic dysplastic kidney

  • C Mark Taylor, Consultant Paediatric Nephrologist

  Dear Editor,

  The power of a systematic review is only as good as the question being posed. In his review of the risk of hypertension in children with multicystic kidney disease (MCKD), Narchi misses the wider context.[1] There may be more than one relationship between the diagnosis of MCKD and blood pressure (BP). Perhaps the component in the mind of the author is that a multicystic dysplastic kidney might in itse...

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  Dear Editor,

  The power of a systematic review is only as good as the question being posed. In his review of the risk of hypertension in children with multicystic kidney disease (MCKD), Narchi misses the wider context.[1] There may be more than one relationship between the diagnosis of MCKD and blood pressure (BP). Perhaps the component in the mind of the author is that a multicystic dysplastic kidney might in itself be a cause of hypertension. This seems unlikely if the affected kidney is non- functioning and contains no renal elements. His review supports this presumption, although exceptions are clearly reported.[2] The majority of non-functioning multicystic dysplastic kidneys involute, so that a proportion of individuals who had MCKD originally are diagnosed later as having unilateral renal agenesis (RA), technically a misnomer in this case. It would make more sense to widen the enquiry to include this category.

  An important consideration is the role of the contralateral kidney in the regulation of BP in these patients. Firstly, the contralateral kidney will prove to be radiologically abnormal in about a quarter of cases of MCKD or RA. Coarse focal scarring, hydronephrosis or hypoplasia would be expected to have an impact on BP depending on the nature of the abnormality.

  Radiologically normal solitary kidneys can also predispose to hypertension. Although they are significantly larger than normal paired kidneys and their complement of nephrons is unknown, there are good reasons to consider that patients with MCKD or RA embark upon life with a reduced number of nephrons. There are data to indicate that a modest reduction in the number of nephrons, even in people with two kidneys, is a risk factor for the development of hypertension.[3,4] This is supported by studies in other species, and in a variety of models.[5,6,7] For example uni-nephrectomy in rat pups and in the ovine foetus induces salt sensitive hypertension that takes time to evolve.

  Blood pressure is a continuous variable in the population and correlations between BP and cardiovascular disease extend well into the normal range.[8] Therefore the separation of hypertension from normotension is somewhat arbitrary, and the qualitative end point does not serve the analysis very well, particularly in young subjects who have yet to disclose overt hypertension however defined. A correlation with the quantitative variable of blood pressure is more relevant. Omitted from the review is the observation that a subtle but significant increase in BP can be found in children with a solitary kidney using 24 hour ambulatory BP recording.[11] Moreover, there are enough follow up studies of adults with either unilateral RA or surgical loss of one kidney in childhood to suggest an increase risk of hypertension even when the remaining kidney is thought to be “normal”[9,10] It clearly takes time, certainly more than 20 years, for this end point to be reached.

  Narchi’s plea for long term follow-up is a sound one but should not be based on the premise that there is no information on outcome. On the contrary, there is enough positive information to indicate that individuals with MCDK, RA or renal loss for other reasons early in life deserve BP monitoring in adulthood, especially if there are additional risk factors such as obesity.[12]

  C Mark Taylor
  Department of Nephrology, Birmingham Children’s Hospital, B4 6NH, UK.
  Email: cm.taylor@bch.nhs.uk

  Competing interests: none

  References:

  1. Narchi H. Risk of hypertension with multicystic kidney disease: a systematic review. Arch Dis Child 2005; 90: 921-924.

  2. Webb NJA, Lewis MA, Bruce J, Gough DCS, Ladusans EJ, Thomson APJ, Postlethwaite RJ. Unilateral multicystic dysplastic kidney: the case for nephrectomy. Arch Dis Child 1977; 76: 31-34.

  3. Brenner BM, Mackenzie HS. Nephron mass as a risk factor for progression of renal disease. Kidney Int Suppl 1997; S63: S124-127.

  4. Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with primary hypertension. N Engl J Med 2003; 348: 101-8.

  5. Cullen-McEwen LA, Kett MM, Dowling J, Anderson WP, Bertram JF. Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice. Hypertension 2003; 41: 335-340.

  6. Woods LL, Weeks DA, Rasch R. Hypertension after neonatal uninephrectomy in rats precedes glomerular damage. Hypertension 2001; 38: 337-342.

  7. Moritz KM, Wintour EM, Dodic M. Fetal uninephrectomy leads to postural hyperension and compromised renal function. Hypertension 2003; 39: 1071-1076.

  8. MacMahon S, Neal B, Rodgers A. Hypertension – time to move on. Lancet 2005; 365: 1108-9.

  9. Mei-Zahav M, Korzets Z, Cohen I, Kessler O, Rathaus V, Wolach B, Pomeranz A. Ambulatory blood pressure monitoring in children with a solitary kidney – comparison between unilateral renal agenesis and uninephrectomy. Blood Pressure Monitoring 2001; 6: 263-267.

  10. Argueso LR, Ritchey ML, Boyle ET, Milliner DS, Bergstralh EJ, Kramer SA. Prognosis of patients with unilateral renal agenesis. Pediatr Nephrol 1992; 6: 412-416.

  11. Baudoin P, Provoost AP, Molenaar JC. Renal function up to 50 years after unilateral nephrectomy in childhood. Am J Kid Dis 1993; 21: 606-611.

  12. Gonzales E, Gutierrez E, Morales E, Hernandez E, Andres A, Bello I, Diaz-Gonzales R, Leiva O, Praga M. Factors influencing the progression of renal damage in patients with unilateral renal agenesis and remnant kidney. Kidney Int 2005; 68: 263-270.

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  Conflict of Interest:
  None declared.

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