3: Renal and Bladder Physiology

This chapter will take approximately 20 minutes to read.

By Eric G. Benz, MD 1, 2  &
  1. Department of Pediatrics, Division of Nephrology, Children's Hospital Colorado, Aurora, CO, USA
  2. University of Colorado, School of Medicine, Aurora, CO, USA

Introduction

The kidneys play an essential role in the normal health and development of children. The nephron is the functioning unit of the kidney, with each kidney containing ~500,000–1,000,000 nephrons. Cumulatively, the basic processes of the nephron are 1) filtration, 2) reabsorption, and 3) secretion.

Figure 1
Figure 1 The nephron is the functioning unit of the kidney and is composed of the glomerulus, proximal tubule, loop of Henle, distal convoluted tubule and collecting duct.

Each nephron has 5 main parts: 1) the glomerulus, 2) the proximal tubule, 3) the loop of Henle, 4) the distal convoluted tubule, and 5) the collecting ducts (Figure 1). The glomeruli (‘filters’) have both charge and size selectivity and filter plasma across the endothelial (capillary), glomerular basement membrane, and epithelial (podocyte) layers. (See below regarding assessment of filtration.) The proximal tubule (‘workhorse’) is where approximately 85% of reabsorption occurs—including sodium, water, amino acids, and glucose. The loop of Henle allows for dilution and subsequent concentration of urine via the counter current multiplier. The distal convoluted tubule contains the macula densa which is critical for juxtaglomerular feedback with subsequent autoregulation of renal blood flow. Autoregulation allows for a fairly constant glomerular filtration rate (GFR) under normal physiological circumstances. Finally, the collecting ducts respond to anti-diuretic hormone (ADH), which allows for concentration of urine, as well as aldosterone which allows for secretion of potassium.

Summary of Kidney Function

  1. Filtration of nitrogenous waste
  2. Volume/blood pressure control
  3. Electrolyte balance
  4. pH regulation
  5. Vitamin D conversion
  6. Epogen production

Beyond filtration, the kidneys also control volume and blood pressure (via both response to ADH as well as the renin angiotensin aldosterone system), regulate electrolyte balance, help regulate serum pH, convert inactive 25-hydroxy vitamin D to active 1,25-dihydroxyvitamin D, and secrete epogen.

Assessing Renal Function

Despite the complexity of filtration, reabsorption and secretion along the nephron, assessment of nephron function can be simplified into two parts: filtration (glomeruli) and tubular function.

Assessment of Filtration

Glomerular filtration rate (GFR) is the rate at which plasma is cumulatively filtered through the nephrons. After filtration, most of the filtered load is reabsorbed along the nephron. In pediatrics, the Schwartz equation is most commonly used to estimate GFR (eGFR) in children.1 The Schwartz equation (Figure 2) is based on serum creatinine as well as the child’s height. While a normal GFR in adults is ~120 mL/min/1.73 m2, in pediatrics a normal GFR varies depending on a child’s age. Typically, a full-term neonate’s initial GFR is only ~30 mL/min/1.73 m2 while a premature neonate’s initial GFR can be even lower ~15 mL/min/1.73 m2.2 Regardless of gestational age, GFR roughly doubles within 2 weeks of age because of decreasing vascular resistance with a resultant increase in renal blood flow and perfusion. GFR then continues to increase (corrected for body surface area) and reaches adult norms at about 19 months of age. Serum creatinine is the easiest way to estimate GFR but has drawbacks, as serum creatinine is affected by muscle mass, body habitus, and underlying medical conditions.

Figure 2
Figure 2 The Schwartz equation is a simple bedside formula to estimate glomerular filtration rate in children.

Cystatin C

While creatinine has been the mainstay laboratory value to assess renal function, a new molecule to estimate GFR has been increasingly utilized. Cystatin C is a molecular housekeeping protein produced by all nucleated cells that is excreted at a constant rate in the urine and not reabsorbed by the nephron. Equations have now been created for both children and adults to measure the serum level of Cystatin C and use that to assess eGFR. Additionally, it has been shown that certain populations, specifically those with poor muscle mass/muscular dystrophies and children with spina bifida, have more accurate estimates of their GFR using Cystatin C alone.3,4 Cystatin C does have pitfalls, as it can be up or down regulated in certain clinical scenarios. Children with poorly managed thyroid dysfunction or those on steroids can affect their serum cystatin C and thus make it a poor marker for measuring eGFR in those populations.5 Additionally, like creatinine, most eGFR calculations using Cystatin C are only validated in children 1–2 years and greater, due to GFR not maturing until about 2 years of age.

Estimating Equations for Glomerular Filtration Rate

In addition to the Schwartz equation, several other equations to estimate GFR have been developed using either creatinine, cystatin C, or both in combination. One example is the Zappitelli equation, which provides a cystatin C only eGFR calculation for children 1–18 years old.6 Additionally, CKiD (Chronic Kidney Disease in Children cohort study) has published updated equations to estimate GFR in children with chronic kidney disease from ages 1–25 using either Creatinine, Cystatin C, or a combination of both.7 Consideration of the study cohort is important to ensure appropriate interpretation of the estimated GFR (Table 1). Children who have an abnormal eGFR should be referred to a pediatric nephrologist for further evaluation, work-up, and management.

Table 1 A sample of various equations to estimate eGFR in children using serum creatinine, serum cystatin C, or both serum measures.

Estimated GFR (eGFR) Equation Study Population Calculator
Creatinine only    
Schwartz equation (k=0.55)8 Children 1–21 with CKD —
Modified bedside Schwartz eq. (k=0.413)9 Children 2–18 with CKD Link to modified Schwartz calculator
Cystatin C only    
Zappitelli equation6 Children 1–18 with CKD or kidney transplant —
Creatinine, Cystatin C, or combined    
CKiD U25 equation7 Children 1–25 with CKD Link to CKiD U25 calculator
CKD-Epi equation10 Adults ≥18 with and without CKD Link to CKD-Epi calculator

Clinical Pearl

  • In children with spina bifida, Cystatin C has been shown to be a better serum marker of eGFR compared to creatinine. Consider sending serum Cystatin C, if able, at least annually on children with spina bifida after the age of 2 years to monitor their kidney function and refer to a pediatric nephrologist if the eGFR is abnormal.4

Assessment of Tubular Function

Tubular function can be assessed via electrolyte balance as well as the ability to concentrate and dilute urine. Tubulopathies can often be successfully diagnosed via interpretation of electrolyte abnormalities.11 For example, tubular wasting of sodium, phosphorus, potassium, amino acids and glucose should precipitate an evaluation for Fanconi syndrome. Fanconi syndrome occurs when there is a global defect in proximal tubular function with resultant urinary losses of the filtered load that would normally be reabsorbed.12 Children with Fanconi syndrome typically present with failure to thrive.

As stated previously, urinary concentration occurs in the collecting ducts in the presence of, and renal response to anti-diuretic hormone (ADH). The concentration gradient that allows for concentrating the urine is set up in the loop of Henle, which first dilutes urine. Urine can be diluted to ~50 mOsm/kg and concentrated to ~1200 mOsm/kg. Full concentrating ability takes several months to develop, and a typical full-term neonate can only concentrate their urine to ~500 mOsm/kg. This concentrating defect of infancy is a result of an immature counter current multiplier as well as relative tissue insensitivity to ADH.13

Clinical Pearl

  • To estimate urine osmolality (Uosm), multiply the last two digits of the urine specific gravity by 30.
  • Example: Urine specific gravity of 1.020
  • Estimated Uosm = 20 × 30 = 600 mOsm/kg

In general, if serum electrolytes (sodium, potassium, phosphorus, calcium, bicarbonate) are within normal limits, the urinalysis indicates that the child can concentrate or dilute their urine, and there is no tubular wasting of glucose or amino acids/protein, then tubular function can be assessed as normal.

Tubular Function by Age

Like GFR, tubular function takes time to mature—this also coincides with the increasing GFR over the first few years of life. Typical values for urine electrolytes and serum electrolytes change over time, with some tubular function taking years to reach full maturity. The ability to concentrate the urine takes nearly a year to mature, making infants at greater risk for dehydration. Water excretion also takes time to mature, making it very important to provide hypotonic fluids to infants (i.e., breastmilk or formula) and not free water to prevent hyponatremia. Sodium reabsorption is initially poor in newborns, making the FENa higher in newborns if assessing for pre-renal acute kidney injury. Additionally, serum potassium levels are higher in newborns due to poor distal tubular secretion of potassium, which matures over the first 2 weeks of life. Serum bicarbonate levels are also lower in the newborn period due to poor reabsorption of bicarbonate in the proximal tubule and increased overall acid production in infants. Lastly, urine calcium excretion in increase in infants and slowly decreases until 10 years of age, making normal urine calcium/creatinine ratios decrease as the children get older.

Clinical Pearl

  • Many children with CKD due to congenital anomalies of the kidney and urinary tract (CAKUT) may never fully be able to concentrate their urine, meaning that they still may have brisk urine output when clinically dehydrated. Be sure to assess patients with underlying kidney disease for other signs/symptoms of dehydration other than relying on urine output. Have a low threshold to provide IV or oral rehydration during acute illnesses.

Acute Kidney Injury

Acute kidney injury (AKI) refers to a sudden decrease in glomerular filtration rate. AKI is typically reversible, however there is a growing appreciation that AKI can lead to chronic kidney disease (CKD). There are several staging classifications of AKI, such as the p-RIFLE criteria and KDIGO criteria, which stratifies AKI in children.14 The KDIGO criteria has been adopted as the more common way of assessing AKI in the literature in recent years. It classifies AKI into stage 1, 2, and 3 based on rise of serum creatinine or decrease in urine output.15 Even more recently, there are propositions to adapt a modified KDIGO criteria to neonatal AKI.16

Table 2 KDIGO classification of AKI in children using either serum creatinine or urine output.15

AKI Stage Serum creatinine Urine output
Stage 1 1.5–1.9× baseline or ≥ 0.3 mg/dL (≥ 26.5 umol/L) increase < 0.5 mL/kg/hr for 6–12 hrs
Stage 2 2.0–2.9× baseline < 0.5 mL/kg/hr ≥12 hrs
Stage 3 3.0× baseline or increase in sCr to ≥ 4.0 mg/dL (≥ 353.6 umol/L) or initiation of RRT < 0.3 mL/kg/hr for ≥24 hrs or anuria for ≥ 12 hours

In the setting of AKI, it is important to understand that a rise in creatinine typically appears only after significant renal dysfunction has begun, and often several days following the initial insult - well into the process of kidney injury. There are now different AKI biomarkers being studied and implemented into clinical practice to detect AKI earlier in the process before the creatinine rise.17 Neutrophil gelatinase associated lipoprotein (NGAL) has been the most promising marker of early AKI so far and is starting to be offered as a clinical test in some hospitals. Practice patterns involving NGAL vary, but it is often used to detect AKI prior to changes in serum creatinine or urine output, especially in the critical care setting.18

Etiology of AKI

A typical starting point to determine the etiology of AKI includes an assessment of prerenal, intrinsic renal, or obstructive processes. Obstruction can be ruled out via imaging, typically via renal and bladder ultrasound. Prerenal and intrinsic etiologies of kidney injury will be discussed herein.

Prerenal Azotemia

Prerenal azotemia refers to a decrease in GFR secondary to poor renal perfusion, often in the setting dehydration or volume loss. Patients who are prerenal will often exhibit oliguria (urine output <0.5 mL/kg/hr in children, <500 mL/day in adults) and will demonstrate signs and symptoms of dehydration (tachycardia, dry mucus membranes, hypotension, increased skin turgor). Assessment of a urinary fractional excretion of sodium (FENa) will be very low (<1%) (Table 3), indicating that the renal tubules are appropriately reabsorbing sodium. Blood urea nitrogen (BUN) is usually elevated in prerenal azotemia. This is a result of an increase in reabsorption of sodium in the proximal tubule which results in a passive reabsorption of both water and urea nitrogen. Thus, the patient’s serum BUN to creatinine ratio will be elevated in prerenal azotemia. The treatment of prerenal azotemia is intravascular volume repletion, typically via normal saline boluses. After attaining euvolemia, it is important not to continue to bolus with excessive fluids, as prerenal azotemia can lead to acute tubular necrosis (see below) if the injury is long-standing, and in such cases, the patient may not be able to make urine. In this case, excessive fluid resuscitation can lead to hypervolemia with resultant hypertension, edema, and respiratory distress.

Intrinsic Renal Failure

Intrinsic renal failure refers to AKI that is not secondary to prerenal or obstructive causes. It is most helpful to refer to the construct of the nephron when considering intrinsic AKI as this correlates with the various etiologies: 1) vascular causes; 2) glomerulonephritis; 3) acute tubular necrosis; and 4) acute interstitial nephritis.

Vascular

Vascular causes of AKI are quite common and include any perturbation in blood flow to the kidney—most commonly secondary to medications such as NSAIDs or cyclosporine/tacrolimus, which cause vasoconstriction of the afferent arterioles, or ACE-inhibitors/ARBs such as lisinopril, which cause vasodilation of the efferent arterioles.19 For this reason, it is critical to remember that NSAIDs, including ketorolac and ibuprofen are completely contraindicated in any patient who is dehydrated, see Figure 3.20 Thrombotic microangiopathies (TMA) such as the hemolytic uremic syndrome can also be classified as a vascular cause of AKI. In TMA, platelet rich thrombi form in the capillary loops of the glomeruli, restricting blood flow and leading to a decrease in GFR.

Figure 3
Figure 3 Mechanism of acute kidney injury in the setting of dehydration with NSAID exposure. (A) normal autoregulation in the setting of dehydration where decreased effective circulating volume leads to vasodilation of the afferent arterioles via prostaglandins, while the efferent arterioles are constricted by angiotensin II (via the renin-aldosterone-angiotensin system). (B) Impairment of autoregulation by NSAIDs.

Glomerulonephritis

Glomerulonephritis (GN) can typically be diagnosed quite readily with evaluation of the urine sediment showing red blood cell casts. The hallmarks of acute glomerulonephritis include hypertension, edema and AKI. The differential diagnosis of glomerulonephritis can be divided into two main categories based on serum complement levels—hypocomplementemic or normocomplementemic. Hypocomplementic GNs include post-infectious GN, systemic lupus erythematosis, and membranoproliferative GN. Normocomplementemic GNs include IgA nephropathy, Alport’s syndrome, and the ANCA vasculitides. Treatment of acute GN depends on the underlying cause, other than in the self-resolving illness of post-infectious GN, most GNs require treatment with immunosuppressive therapy.

Acute Tubular Necrosis

Acute tubular necrosis (ATN) is the most common cause of AKI. ATN is usually caused either by ischemia-reperfusion injury, or exposure to nephrotoxic medications. Patients with ATN are typically oliguric and their urine sediment may demonstrate muddy brown or granular casts. In contrast to prerenal azotemia, patients with ATN have a FENa >1% (Table 3).

Table 3 Comparison of prerenal azotemia to acute tubular necrosis (ATN).

  Prerenal Azotemia ATN
Urine volume ↑ usually ↓
BUN/creatinine >20/1 ~10/1
Urine [Na*) <20 mEg/L >40 mEg/L
FENa <1% >2%
Urine osm >500 mOsm/kg ~300 mOsm/kg
Urine sediment hyaline or granular casts brown casts, renal tubular cell casts
Course reversible with correction of underlying cause oliguria x days, gradual recovery over days to wks

Treatment of ATN includes renal rest—maintaining euvolemia and avoidance of nephrotoxic medications. Some studies have shown the use of theophylline helps reduce AKI/ATN in neonates caused by perinatal asphyxia, but decision to administer this drug should be done in collaboration with a pediatric nephrologist.21 In oliguric patients, strict attention to fluid balance is necessary to maintain euvolemia. Recovery from ATN may take days to weeks, and often the oliguria transitions to polyuria with a persistently elevated serum creatinine. When the patient becomes polyuric, it is critical to maintain adequate hydration. Until the renal tubules recover, the patient is unlikely to be able to concentrate their urine, and as such they are at risk for developing prerenal azotemia with a potential secondary renal hit if intake is not increased to keep up with output.

Clinical Pearl
  • A good rule of thumb when dealing with such patients is to obtain daily weights, strict ins and outs and to maintain the euvolemic patient on 1/3 × their maintenance fluid plus 1:1 replacement of urine output. The 1/3 × maintenance approximates the patient’s insensible fluid losses, while the replacement of urine output will work to maintain euvolemia in both oliguric and polyuric patients.
  • In patients who are NPO, typical fluids can be 5% dextrose 0.9% normal saline if they are otherwise normal children without underlying kidney dysfunction.22 However, serum electrolytes should be followed closely while on IV fluids. Polyuric patients may need addition of potassium to their intravenous fluids. Patients who have loose stools may need additional repletion for stool losses, including the addition of bicarbonate to the fluids. Children with kidney dysfunction should be considered case by case but starting fluids containing 5% dextrose 0.45% normal saline to reduce their salt load should be considered.
Acute Interstitial Nephritis

Acute interstitial nephritis (AIN) is an underappreciated cause of AKI. AIN is often triggered by a reaction to an offending medication and is sometimes referred to as allergic interstitial nephritis. AIN may also be triggered by a viral infection; however most causes of AIN are idiopathic. While historically, urine was often sent for evaluation of eosinophils, eosinophiluria is neither sensitive nor specific for diagnosing AIN. As such, AIN can be diagnosed clinically in the setting of a patient with non-oliguric AKI with a bland urine sediment. Treatment of AIN includes cessation of the offending medication when clinically possible. AIN can also be treated with steroids, however, if the cause is medication-related, kidney injury may return once the steroids are discontinued. A rare but associated disease is tubulointerstitial nephritis and uveitis (TINU) syndrome.23 These patients have both AIN and uveitis. TINU is often responsive to steroids, however, the uveitis requires ophthalmologic evaluation and treatment separate and in addition to renal evaluation and treatment.24

Clinical Pearl
  • Patients with an intra-abdominal urinary leak can inappropriately be diagnosed with AKI. In these patients, their serum creatinine rises secondary to reabsorption of urine creatinine across the peritoneal membrane with a resultant rise in serum creatinine. In this case, serum creatinine no longer reflects renal filtration. The diagnosis should be suspected in any patient with new development of ascites in the setting of a rising creatinine, who is at risk for urinary leak (i.e. recent surgical procedure).
Indications for Dialysis

There is no current treatment for AKI other than supportive care. Renal replacement therapy may be required if optimal medical management does not suffice. Indications for initiating acute dialysis include volume overload, electrolyte derangements, metabolic acidosis or uremia.

Chronic Kidney Disease

Chronic kidney disease (CKD) refers to either laboratory or radiographic evidence of kidney disease that progresses beyond 3 months. There are five stages of CKD, based on estimated glomerular filtration rate (Figure 4). In children with CKD, specific equations (noted above) are used to estimate their eGFR in order to stage the degree of CKD. Unlike adult patients who are often followed by their primary care provider throughout the early stages of CKD, all children with CKD should be followed by a pediatric nephrologist for subspecialty care.25 Particular attention is paid to the growth and development of children with CKD. The frequency of nephrology follow-up correlates with the stage of CKD. Of note, GFR reaches its max at around 2 years of age, making it impossible to stage CKD in children less than 2 years of age accurately.

Figure 4
Figure 4 Stages of Chronic Kidney Disease.

Management of Chronic Kidney Disease

Unfortunately, there is no cure for CKD. However, early referral to a pediatric nephrologist can help with management of co-morbidities and delay progression of disease. Routine CKD management includes assessment of staging, blood pressure control, as well as monitoring for anemia, growth delay, and metabolic bone disease.

Blood Pressure Control

Tight blood control to the 50th% for age, sex and percentile height has been shown to delay progression of CKD.26 ACE-inhibitors and ARBs are often the preferred agent to control blood pressure as they also protect against glomerular hyperfiltration. Blood pressure should be measured at all clinic visits, preferable manually, in patients with or at risk for CKD. Referral to a pediatric nephrologist for further evaluation and possibly a 24 hour ambulatory blood pressure monitor study should be made for any abnormal clinic blood pressure in a child with CKD.

Anemia of Chronic Kidney Disease

Children with CKD have several reasons to be anemic—including erythropoietin deficiency and increased hepcidin levels which leads to poor utilization of iron stores.27 Patients with CKD should have routine CBCs to monitor for the development of anemia. If and when they become anemic, iron stores should be checked and normalized. Patients who remain anemic despite adequate iron stores should be started on erythropoiesis stimulating agents such as epoetin alfa or darbepoetin alfa.25

Metabolic Bone Disease

Formerly referred to as secondary hyperparathyroidism, metabolic bone disease encompasses not only secondary hyperparathyroidism, but also bone mineralization and vascular calcifications. MBD is often the most challenging aspect in managing children with CKD and is unfortunately the reason for a significant amount of morbidity and mortality in our pediatric patients with CKD. MBD leads to increased cardiovascular disease, the leading cause of death in patients with CKD. Indeed, a pediatric patient with end stage renal disease has the cardiovascular risks of a patient in their 70s.28 Management includes maintaining adequate stores of 25-hydroxy vitamin D, maintaining normocalcemia and normal serum phosphorus levels, and supplementation of active 1-25-dihydroxyvitamin D.29,30 It is often quite difficult for patients to comply with the prescribed phosphorus binders which are taken with meals, and often cause gagging and discomfort. This is particularly difficult in young children, with whom mealtime can already be quite challenging.

Growth

Children with CKD often have difficulty with growth and development. A multidisciplinary team including a renal dietician is critical for proper monitoring of nutritional intake and growth. Unlike adults with CKD, children do not have a reduced protein limit, as they require protein for growth. We therefore recommend children with CKD obtain the recommended daily allowance of protein. Linear growth is particularly challenging because of a relative tissue insensitivity to growth hormone. Infants and toddlers with CKD often require gastrostomy tubes for either medication administration and/or supplemental formula feeds. Special renal formulas that support growth and nutrition while limiting potassium and phosphorus are often required. Supplemental growth hormone is indicated in patients not growing well linearly despite adequate caloric intake. Unfortunately, many families decline growth hormone treatment in order to save their child a daily injection, however quality of life studies have demonstrated that adult height positively correlates with quality of life.31

Renal Replacement Therapy

Children who are progressing to stage V CKD require evaluation for renal replacement therapy. RRT can be in the form of either peritoneal dialysis (PD), hemodialysis (HD), or kidney transplantation. For patients who have a potential living donor, preemptive transplantation may be a suitable and often desirable option. Evaluation of a living donor make take several months, so such a preemptive transplantation should begin while the patient is still in stage IV CKD, if possible. Similarly, introducing the concepts of dialysis and transplantation at an earlier stage, such as stage III often benefits the family and patient so they can begin to think about dialysis modalities versus preemptive transplantation.

The term ‘dialysis’ refers to two separate mechanisms: 1) diffusion of solutes across a semipermeable membrane, and 2) removal of fluid via ultrafiltration.

Peritoneal Dialysis

In peritoneal dialysis, dialysate is placed in the peritoneal cavity. The peritoneal membrane acts as the semipermeable membrane and allows solutes to flow across and down their concentration gradient. Ultrafiltration is controlled via the addition of dextrose to the dialysate fluid. By increasing the dextrose concentration to the dialysate, the osmotic gradient increases, thereby pulling more fluid from the patient into the peritoneal cavity. The fluid is then drained from the peritoneum. Most pediatric patients undergo home PD at night while they are asleep. In this way, they undergo several cycles, typically anywhere from 6–12 cycles. The PD prescription therefore includes the fill volume, dwell time, and dialysate to be used (including the dextrose concentration). The additional volume that is drained during each cycle drain is tallied and the total accumulated over the treatment is referred to as the ultrafiltrate (UF) volume. Of note, patients may retain fluid during PD and this typically indicates they might have been hypovolemic at the initiation of the treatment. Home PD requires extensive training of the caregivers with frequent communication with their nephrology center. Caregivers are expected to keep daily logs of pre- and post- treatment weights, blood pressures, dialysate used and UF obtained. Many patients have a sliding scale prescription such that the dextrose concentration can be adjusted based on their pre-dialysis weight and blood pressure.32

Peritonitis is the main risk in patients who undergo PD. Caregivers are taught to recognize the signs and symptoms of peritonitis and are also trained to obtain a peritoneal effluent for cell count and culture prior to initiating intraperitoneal antibiotics. PD patients on antibiotics should always receive anti-fungal prophylaxis to prevent fungal peritonitis. Fungal peritonitis is both difficult to diagnosis as well as treat, and unfortunately requires removal of the PD catheter and has a high risk of scarring the peritoneal membrane.

Membrane failure can result from fungal peritonitis, recurrent bacterial peritonitis, or may be a result of glycosylation of the membrane from prolonged exposure to the dextrose in the dialysate. Routine peritoneal membrane tests are performed by their nephrologist to assess membrane characteristics and to help adjust PD orders over time.

Hemodialysis

In hemodialysis, the patient’s blood is circulated thru a dialysis machine containing an HD filter. Most filters are now hollow-fiber capillary membranes. Each fiber is hollow and allows blood to flow thru the tube, in countercurrent to dialysate flowing around the fibers. This design allows for a large surface area where-in the fibers are the semi-permeable membrane that allow for flow of solutes across the membrane and down their concentration gradient. UF is attained via negative pressure applied by the dialysis machine. The UF rate is limited by patient size, blood pressure and symptoms. Dialysis access can be challenging in pediatric patients. Often, fistula access is limited by patient size and vasculature. As a result, many pediatric patients have the additional risk of central line access, known to have an increased risk of infection above fistulas and grafts.25

The choice of dialysis modality is made based on a combination of the child’s current medical status, underlying disease, family support and often, geographic location (i.e. distance from a hemodialysis center that will treat children). Past episodes of peritonitis or surgical procedures that have left adhesions may limit the option to pursue peritoneal dialysis. Certainly, peritoneal dialysis requires more social stability as well as time, energy and commitment from the child’s caregivers. Despite these additional responsibilities, PD is often a preferred choice as it allows the child to continue to go to school. Alternatively, hemodialysis (HD) is a good alternative for patients who have either failed PD, or who’s family may be unable to provide PD at home. Home hemodialysis is also an option offered by some pediatric dialysis program for families who would be equipped for PD at home, but the patient is not a suitable PD candidate.

Regardless of the dialysis modality chosen, the goal of every pediatric nephrology program is to successfully transplant their pediatric patients with ESRD. The life expectancy of children with ESRD on dialysis is 50 years shorter than healthy age-matched cohorts, compared to 15 years shorter following transplantation.28 Transplantation evaluation includes psychosocial evaluation and at times, transplantation is delayed or put on hold if the child is not interested or is deemed to be a poor candidate based on non-compliance with prescribed therapies.

Suggested Readings

  1. Atkinson MA, Ng DK, Warady BA, Furth SL, Flynn JT. The CKiD study: overview and summary of findings related to kidney disease progression. Pediatr Nephrol 2021; 36 (3): 527–538. DOI: 10.1007/s00467-019-04458-6.
  2. Schwartz GJ, Work DF. Measurement and Estimation of GFR in Children and Adolescents. Clin J Am Soc Nephrol 2009; 4 (11): 1832–1843. DOI: 10.2215/cjn.01640309.
  3. Zeidel ML, Hoenig MP. Cardiac Physiology for the Clinician. Jama 2014; 235 (26): 2865. DOI: 10.1001/jama.1976.03260520057032.

References

  1. Schwartz GJ, Work DF. Measurement and Estimation of GFR in Children and Adolescents. Clin J Am Soc Nephrol 2009; 4 (11): 1832–1843. DOI: 10.2215/cjn.01640309.
  2. Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol 2007; 22 (11): 1839–1848. DOI: 10.1007/s00467-006-0358-1.
  3. Fox JA, Dudley AG, Bates C, Cannon GM. Cystatin C as a Marker of Early Renal Insufficiency in Children with Congenital Neuropathic Bladder. J Urol 2014; 191 (5s): 1602–1607. DOI: 10.1016/j.juro.2013.09.093.
  4. Dangle PP, Ayyash O, Kang A, Bates C, Fox J, Stephany H, et al.. Cystatin C-calculated Glomerular Filtration Rate–A Marker of Early Renal Dysfunction in Patients With Neuropathic Bladder. Urology 2017; 100: 213–217. DOI: 10.1016/j.urology.2016.08.011.
  5. Filler G, Lee M. Educational review: measurement of GFR in special populations. Pediatr Nephrol 2018; 33 (11): 2037–2046. DOI: 10.1007/s00467-017-3852-8.
  6. Zappitelli M, Parvex P, Joseph L, Paradis G, Grey V, Lau S, et al.. Derivation and Validation of Cystatin C–Based Prediction Equations for GFR in Children. Am J Kidney Dis 2006; 48 (2): 221–230. DOI: 10.1053/j.ajkd.2006.04.085.
  7. Pierce CB, Muñoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney Int 2021; 99 (4): 948–956. DOI: 10.1016/j.kint.2020.10.047.
  8. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Aktuelle Urol 1976; 35 (03): 195–196. DOI: 10.1055/s-2004-830943.
  9. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al.. New Equations to Estimate GFR in Children with CKD. J Am Soc Nephrol 2009; 20 (3): 629–637. DOI: 10.1681/asn.2008030287.
  10. Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, et al.. New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race. N Engl J Med 0AD; 385 (19): 1737–1749. DOI: 10.1056/nejmoa2102953.
  11. Ariceta G, Rodrı́guez-Soriano Juan. Inherited Renal Tubulopathies Associated With Metabolic Alkalosis: Effects on Blood Pressure. Semin Nephrol 2006; 26 (6): 422–433. DOI: 10.1016/j.semnephrol.2006.10.002.
  12. Louis-Jean S, Ching PR, Wallingford A. Distal Renal Tubular Acidosis in Sjögren’s Syndrome: A Case Report. Cureus 1961; 16: 609–621. DOI: 10.7759/cureus.10962.
  13. Gardner SL, Carter BS, Ensman-Hines MI, Niermeyer S. Merenstein & Gardner’s handbook of neonatal intensive care nursing: an interprofessional approach. .
  14. Sutherland SM, Byrnes JJ, Kothari M, Longhurst CA, Dutta S, Garcia P, et al.. AKI in Hospitalized Children: Comparing the pRIFLE, AKIN, and KDIGO Definitions. Clin J Am Soc Nephrol 2015; 10 (4): 554–561. DOI: 10.2215/cjn.01900214.
  15. Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin Pract 2012; 120 (4): c179–c184. DOI: 10.1159/000339789.
  16. Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, et al.. Neonatal Acute Kidney Injury. Pediatrics 2015; 136 (2): e463–e473. DOI: 10.1542/peds.2014-3819.
  17. Sandokji I, Greenberg JH. Novel biomarkers of acute kidney injury in children. Curr Opin Pediatr 2020; 32 (3): 354–359. DOI: 10.1097/mop.0000000000000891.
  18. Stanski N, Menon S, Goldstein SL, Basu RK. Integration of urinary neutrophil gelatinase-associated lipocalin with serum creatinine delineates acute kidney injury phenotypes in critically ill children. J Crit Care 2019; 53: 1–7. DOI: 10.1016/j.jcrc.2019.05.017.
  19. Goldstein SL, Kirkendall E, Nguyen H, Schaffzin JK, Bucuvalas J, Bracke T, et al.. Electronic Health Record Identification of Nephrotoxin Exposure and Associated Acute Kidney Injury. Pediatrics 2013; 132 (3): e756–e767. DOI: 10.1542/peds.2013-0794.
  20. Musu M, Finco G, Antonucci R. NSAID Nephrotoxicity Revisited: Acute Renal Failure Due to Parenteral Ketorolac. South Med J 2011; 86 (12): 1421–1424. DOI: 10.1097/00007611-199312000-00025.
  21. Bellos I, Pandita A, Yachha M. Effectiveness of theophylline administration in neonates with perinatal asphyxia: a meta-analysis. J Matern Fetal Neonatal Med 2021; 34 (18): 3080–3088. DOI: 10.1080/14767058.2019.1673722.
  22. Feld LG, Neuspiel DR, Foster BA. Clinical Practice Guideline: Maintenance Intravenous Fluids in Children. Pediatric Clinical Practice Guidelines &Amp; Policies 2018; 142 (6): 375–388. DOI: 10.1542/9781610026086-part01-21.
  23. Vanhaesebrouck P, Carton D, De Bel C, Praet M, Proesmans W. Acute Tubulo-Interstitial Nephritis and Uveitis Syndrome (TINU Syndrome). Nephron 2000; 40 (4): 418–422. DOI: 10.1159/000183511.
  24. Hayashi A, Takahashi T, Ueda Y, Sato Y, Okamoto T. Long-term clinical characteristics and renal prognosis of children with tubulointerstitial nephritis and uveitis syndrome. Pediatr Nephrol 2021. DOI: 10.1007/s00467-021-04956-6.
  25. Lamb EJ, Levey AS, Stevens PE. The Kidney Disease Improving Global Outcomes (KDIGO) Guideline Update for Chronic Kidney Disease: Evolution not Revolution. Clin Chem 2013; 59 (3): 462–465. DOI: 10.1373/clinchem.2012.184259.
  26. Group ET, Wuhl E, Trivelli A. Foreign Article Review : Strict Blood-Pressure Control and Progression of Renal Failure in Children. Nihon Shoni Jinzobyo Gakkai Zasshi 2009; 23 (1): 54–55. DOI: 10.3165/jjpn.23.54.
  27. Atkinson MA, Kim JY, Roy CN, Warady BA, White CT, Furth SL. Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort. Pediatr Nephrol 2015; 30 (4): 635–643. DOI: 10.1007/s00467-014-2991-4.
  28. Mitsnefes MM. Cardiovascular Disease in Children with Chronic Kidney Disease. Adv Chronic Kidney Dis 2012; 12 (4): 397–405. DOI: 10.1053/j.ackd.2005.07.005.
  29. Bakkaloglu SA, Wesseling-Perry K, Salusky IB. Chronic kidney disease-mineral and bone disorder (CKD-MBD) in children. The Spectrum of Mineral and Bone Disorders in Chronic Kidney Disease 2013; 3 (2): 485–507. DOI: 10.1093/med/9780199559176.003.028.
  30. Kumar J, McDermott K, Abraham AG, Friedman LA, Johnson VL, Kaskel FJ, et al.. Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort. Pediatr Nephrol 2016; 31 (1): 121–129. DOI: 10.1007/s00467-015-3190-7.
  31. Goldstein SL, Gerson AC, Furth S. Health-Related Quality of Life for Children With Chronic Kidney Disease. Adv Chronic Kidney Dis 2007; 14 (4): 364–369. DOI: 10.1053/j.ackd.2007.07.006.
  32. Warady BA, Schaefer F, Bagga A, Cano F, McCulloch M, Yap H-K, et al.. Prescribing peritoneal dialysis for high-quality care in children. Perit Dial Int 2020; 40 (3): 333–340. DOI: 10.1177/0896860819893805.
  33. Atkinson MA, Ng DK, Warady BA, Furth SL, Flynn JT. The CKiD study: overview and summary of findings related to kidney disease progression. Pediatr Nephrol 2021; 36 (3): 527–538. DOI: 10.1007/s00467-019-04458-6.
  34. Zeidel ML, Hoenig MP. Cardiac Physiology for the Clinician. Jama 2014; 235 (26): 2865. DOI: 10.1001/jama.1976.03260520057032.

Last updated: 2023-02-22 15:40