From diapers to the graduation hat, kidneys have to mature from their infancy, childhood,
and adolescence before reaching adulthood. This crucial journey of kiddy kidneys needs
a favorable environment for growth, development and nourishment so as to graduate
into young adult kidneys at 18 years of age. Caring for such a dynamic phase of kidney
maturation becomes the prime responsibility of the pediatric nephrologist. On account
of the World Kidney Day 2016, that focuses on Kidney disease and children, it is befitting
to look at the unique challenges posed by these pediatric kidneys from an Indian perspective.
The Very Beginning
The critical number
Nephrogenesis begins at 9th week of gestation and continues through 34th–36th weeks
of gestation after which time no new nephrons are formed. With an average of 1 million
nephrons per kidney,[1] it is predicted that there is an increase of 257,426 glomeruli
per kilogram increase in birth weight.[2] Clinical surrogates for low nephron number
and susceptibility to hypertension and renal disease in adulthood are low birth weight,
preterm birth, short stature, low kidney volume, glomerulomegaly, gene polymorphisms,
and maternal gestational hyperglycemia.[3] Exploring the concept of adult diseases
having their roots in childhood, South Asian adults are at high risk for premature
severe chronic kidney disease (CKD)[4
5] and harbor a greater propensity to third-trimester growth restriction which impacts
on the developing kidney, leading to reduced kidney volume.[6] Besides the fact that
India is the cradle for 40% of all low birth weight babies in the developing world,[7]
maternal nutrition including Vitamin A status could influence nephrogenesis and renal
volumes in the newborn.[8]
Developmental pangs
Congenital anomalies of the kidney and urinary tract (CAKUT) are part of a syndrome
or sequence that leads to end-stage renal disease in children. The genetic diagnosis
of CAKUT has proven to be challenging due to genetic and phenotypic heterogeneity
and influence of epigenetic and environmental factors on kidney development.[9
10] Specific renal diseases such as polycystic kidney disease and primary hyperoxaluria,
known to be prevalent in India, progressing to CKD, share an autosomal recessive inheritance.
Consanguineous marriage is a cultural phenomenon that is associated with kidney disease
and is prevalent in many Asian countries[11] including rural India. Consanguinity
and genetic predisposition add to the risk of CAKUT, reflux nephropathy, and urinary
tract obstruction that are major contributors to CKD.
Just born kidneys
Newborn kidneys are immature and susceptible to hypoperfusion, low glomerular filtration
rate, high renal vascular resistance, high plasma renin activity, decreased intercortical
perfusion, and decreased reabsorption of sodium in the proximal tubules.[12]
The paucity of Indian data on neonatal acute kidney injury (AKI) is alarming. Besides
sepsis and hypovolemia, Gupta et al.[13] highlighted perinatal asphyxia as an important
risk factor for neonatal AKI. With limitations in obtaining baseline serum creatinine
values and urine output assessment in neonates, many categorical definitions of neonatal
AKI such as the Neonatal Risk, Injury, Failure, Loss of kidney function and End stage
kidney Disease (nRIFLE), AKI network (AKIN), and modified kidney disease improving
global outcomes criteria (KDIGO) pose challenges in the stratification of levels of
severity and early recognition of AKI in clinical practice.[14]
The Formative Years
An interesting feature of pediatric renal diseases is that there is a difference in
the occurrence of disease with age and variation in the manifestation of the same
disease at different phases of childhood: While tubular disorders predominate during
infancy and early childhood, majority of glomerular diseases are generally seen beyond
the first few years of life. Hypertension, urinary tract infection, and CKD are notorious
to have contrasting clinical manifestations that vary with age.
Challenging signs
As in adults, hematuria, oliguria, and edema are the most striking signs of renal
disease, commonly a signature of glomerular disease. However, in children, many signs
of kidney disease are either hidden or they mimic other systemic diseases. For example,
failure to thrive or growth retardation, recurrent vomiting, and respiratory distress
could be the only signs of CKD or a tubular disorder. Bone deformities and neurological
manifestations could be indicators of underlying tubular disorders.
The Pandora's box on genetics
Molecular genetics and genomic science have opened new challenges in patient care.
In India, Pediatric nephrology has made considerable progress in establishing genetic
analysis for diseases such as nephrotic syndrome and hemolytic uremic syndrome.
The acute kidney injury-chronic kidney disease continuum
The incidence of pediatric AKI (Acute Kidney Injury) in hospitalized children[15]
is as high as 36%. The etiological spectrum ranges from tropical systemic infections,
sepsis with multi-organ dysfunction, and snake envenomation to primary renal diseases.
Use of alternative forms medicine poses an additional challenge. Neonates, who survive
sepsis or asphyxia with neonatal AKI,[16] including urinary tract obstruction, are
at high risk for developing CKD. Systematic monitoring of the AKI-CKD clinical syndrome
is the need of the hour. Sensitization and active assessment of possible sequelae
of AKI that has been proposed by the ASSESS-AKI study[17] need implementation in neonates
and children in our country.
Renal recovery
To ascertain renal recovery in children is a challenge.[18] Glomerular filtration
rate (GFR) increases over the 1st year of life from 15 to 90 ml/min/1.73 m2 resulting
in difficulty in deriving an AKI threshold.[19] The current CKD studies and definitions
exclude children under 1 year of age making the diagnosis of CKD difficult in small
children.[20] Finally, children are born with substantial relative renal reserve,
with more than sufficient clearance capacity in relation to their metabolic output.
As estimated renal function is associated with height in children, linear growth plays
a role in preserving renal function.
The chronic blues
Chronic glomerulonephritis, hypodysplasia, and obstructive uropathies have dominated
the list of causes of pediatric CKD in many developing countries.[21] Advances in
the management strategies and availability of certain immunosuppressive therapies
have helped control common glomerular diseases.[22
23] Though dialysis therapy is considered a bridge to transplantation in children,
we are faced with many challenges related to cardiovascular morbidity, nutrition,
anemia, and bone mineral disease in addition to the issues of financial burden and
quality of life.
The gift of life
Live related and deceased organ renal transplantation in children is gathering momentum
in a few centers across the nation.[24
25
26
27
28] However, the real challenge lies not only in escalating the number of transplants
but more importantly in optimizing the long-term care of the allograft posttransplant.
The overall 5 years and 10 years graft survival are reported to be between 80–86%
and 70–75%, respectively.[24
25
26
27
28] Urological issues and interventions play a vital role in pediatric transplantation.
Focal segmental glomerulosclerosis is a major cause for End Stage Renal Disease, and
we have shown the variation in the genetic polymorphisms among Indian children[29]
with recurrence post renal transplant[30] being an additional economic burden.
Graduation
The graduation day for kidneys is when the adult nephrologist takes over care of young
adult kidneys. The weaning period from the pediatric nephrologist has to be a gradual
process undertaken in Transition Clinics. Care of kidneys in children often demands
a multidisciplinary approach with formal psychosocial counseling services, which may
need focus into adulthood.
Parenting kidneys is just not treating children with kidney disease. The broader perspective
lies in implementing Preventive strategies; Outreach initiatives for prompt and early
diagnosis; Training and collaborations for faculty development and capacity building;
and relevant research programs for holistic renal care - A message that should reverberate
not only on World Kidney Day but on every other day!