Keywords

FormalPara Learning Objectives
  1. 1.

    CAKUT is the leading cause of CKD and ESRD in children and adolescents with the median age patients require RRT of 31 years.

  2. 2.

    The pathogenesis of CAKUT is complex with a monogenic cause identified in approximately 20% of patients. Environmental factors including maternal diabetes, obesity, and exposure to teratogens such as ACE inhibitors are also thought to contribute.

  3. 3.

    Patients with CAKUT may have undergone multiple reconstructive and corrective surgeries as a child including bladder augmentation, ureteric reimplantation, and Mitrofanoff formation. It is essential that nephrologists are familiar with the long-term management and possible complications associated with such conditions.

  4. 4.

    Management of patients with CAKUT requires joint nephrology and urology multidisciplinary input with particular focus on the transition between paediatric and adult services.

1 Introduction

Congenital anomalies of the kidneys and urinary tract (CAKUT) encompass a diverse range of developmental malformations (► Box 56.1) and are an important cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children and young people. Although the majority of CAKUT occur as isolated malformations, a significant number of patients will have familial inheritance, and many cases occur as part of multisystem syndromes. With improvements in foetal screening and early urological management, the number of adults with CAKUT as a cause of CKD is likely to increase. Patients with CAKUT present a variety of clinical and management problems and are often cared for as part of a multidisciplinary team – involving a range of healthcare professionals. This is particularly important for young people making the transition from paediatric care to adult follow-up.

2 Epidemiology

CAKUT occur in approximately 3–6 per 1000 live births and collectively account for 20–30% of all congenital anomalies detected antenatally [1]. CAKUT usually occur in isolation although non-renal anomalies are seen in 30%, and it has been associated with over 200 different syndromes. Renal tract malformations account for up to 50% of all childhood CKD and are the leading cause of paediatric ESRD [2], placing a huge socioeconomic and educational burden on patients and their families. However, CAKUT is not just a paediatric disease; the median age for patients requiring renal replacement therapy (RRT) is 31 years, and as a group, they make up 4–5% of adults requiring RRT [3, 4].

3 Pathogenesis

The embryonic kidney is derived from the intermediate mesoderm and proceeds through three distinct developmental phases; the pronephros, mesonephros, and metanephros (► Box 56.2). The lower urinary tract forms from the endodermal cloaca which develops into the urogenital sinus (early bladder and urethra) and rectum. Urine is produced from 9 weeks, and nephrogenesis continues until approximately 36 weeks. Disruption of the tightly regulated process of renal and urinary tract development results in the many differing clinical manifestations of CAKUT, depending on the timing and location of the disruption. Environmental factors such as pre-gestational maternal diabetes mellitus [5] and obesity [6] have been shown to disrupt normal renal development.

4 Genetics

Approximately 10–15% of patients with CAKUT report a family history, and up to 1 in 4 asymptomatic first-degree relatives have been shown to be affected with ultrasound screening [7]. Over 50 different CAKUT-causing genes affecting nephrogenesis have been reported, but the genotype-phenotype heterogeneity and incomplete penetrance seen means a monogenic cause can be identified in only approximately 20% of patients [1, 8,9,10,11]. Pathogenic variants identified in the transcription factors hepatocyte nuclear factor factor-1-beta (HNF1B) and paired box gene 2 (PAX2) are most frequently identified and are associated with renal cysts and renal hypodysplasia, respectively. ► Box 56.3 details the most frequent monogenic CAKUT syndromes associated with autosomal dominant inheritance that may be seen in the renal clinic.

Genetic testing is not currently routine clinical practice but should be considered if there is a family history of CAKUT or any associated eye, limb, ear, or genital anomalies. Similarly, hypomagnesaemia, deranged liver function tests, or early-onset diabetes in a patient with CAKUT might prompt testing for HNF1B variants which are the most frequent genetic diagnosis associated with CAKUT [12]. A molecular diagnosis can not only confirm a diagnosis for the patient, but also help inform prognosis and enable screening for extra-renal manifestations. In addition, it allows accurate counselling regarding recurrence risk in children as well as potentially permitting renal transplantation from a proven unaffected relative.

5 Clinical Presentation

While the majority of structural malformations are detected by antenatal ultrasound screening, cases may present in childhood with failure to thrive, recurrent urinary tract infection, or as a manifestation of an associated syndrome. Adults with previously undiagnosed CAKUT may also present with abnormal urinalysis, renal stones, hypertension, chronic kidney disease, or as an incidental finding on imaging. Furthermore, it is likely that CAKUT underlies a significant proportion of young adults with ‘unexplained’ chronic kidney disease who may present with ‘small, scarred kidneys’.

5.1 Renal Parenchymal Malformations

  • Bilateral renal agenesis is incompatible with life and is characterized by absent kidneys on antenatal ultrasound, pulmonary hypoplasia, and Potter facies (flattened nose, recessed chin, low-set cartilage-deficient ears); a result of intrauterine compression from oligohydramnios. Siblings have an increased risk of occurrence (3–6%) which increases to 15% with a family history of renal agenesis.

  • Unilateral renal agenesis occurs in 1 in 3000 live births. Typically, there is no ipsilateral ureter, and half of the bladder trigone is absent. In 10% of cases, the adrenal gland is also missing. Genital anomalies are commonly associated, and the remaining solitary kidney is usually hypertrophic and may be dysplastic. Ultrasound screening of first-degree relatives is advised.

  • Renal hypoplasia describes a kidney that is two standard deviations below mean size for age with a reduced number of normally differentiated nephrons. In some cases, this is referred to as oligomeganephronia, a kidney with reduced numbers of enlarged nephrons.

  • Renal dysplasia is characterized by the abnormal differentiation of renal parenchyma and typically produces small, irregular kidneys which may be cystic or multicystic. It may be uni- or bilateral and occurs in 2–4/1000 births. A DMSA isotope scan will show reduced uptake in the dysplastic area.

  • Multicystic dysplastic kidney is a large non-functioning kidney that commonly involutes within the first few years of life. The ureter is absent or atretic, and 10% of patients have a family history.

Tips, Tricks, and Pitfalls: Dysplasia vs. Reflux

Renal dysplasia is often associated with the presence of vesicoureteric reflux (VUR) and controversy still exists as to whether renal scarring in the presence of VUR is congenital or acquired. Progressive scarring and renal failure were once considered chronic parenchymal infection (the so-called chronic pyelonephritis) as a consequence of VUR. However, in the 1980s emphasis was placed on scarring as a result of VUR itself and the progressive nature of the lesion associated with glomerular hyperfiltration, the so-called reflux nephropathy. The emphasis is changing again to the concept that scarring is often a consequence of renal dysplasia and that the reflux is a secondary feature. Thus, irregular kidneys with normal calibre ureters are more likely to be caused by primary dysplasia, and there may be no evidence of VUR.

5.2 Abnormal Embryonic Migration

  • Ectopic kidneys fail to ascend correctly into the retroperitoneal renal fossa during development and can have a variable blood supply. They may remain in the pelvis, cross the midline, fuse (e.g. crossed fused ectopia), or fail to rotate medially. The incidence is approximately 1 in 1000 births and are usually asymptomatic. They may be associated with VUR or other genitourinary abnormalities.

  • Horseshoe kidney is the most common fusion anomaly occurring in 1 in 10,000 live births, with fusion occurring at the lower pole in 90%. It is commonly associated with VUR and UPJO and may present with complications of reflux, obstruction, or stone formation.

5.3 Abnormalities of the Collecting System and Ureters

  • Ureteropelvic junction obstruction (UPJO) is the most common cause of antenatally detected hydronephrosis and describes a partial or intermittent total blockage of urine where the ureter enters the kidney. It occurs in 1 in 500 live births. The abnormality is most commonly a congenital ureteric defect but occasionally may be due to extrinsic compression from an aberrant blood vessel or proximal ureteric kinking. Surgical intervention is indicated for pyelonephritis, renal stones, pain, or renal impairment. Occasionally a brisk diuresis (e.g. following consumption of alcohol or caffeine) may precipitate symptoms.

  • Duplex collecting systems may be partial or complete and are the most common congenital anomaly of the urinary tract seen in up to 5% of the population in autopsy studies. They are more common in girls. Ectopic ureters are frequently associated with duplex systems and arise from the upper moiety. In males they are always supra-sphincteric but may insert into the posterior urethra, vas, or seminal vesicle. In females they may be either supra-sphincteric or sub-sphincteric in the urethra, uterus, or distal vagina. Ectopic ureters tend to be associated with a dysplastic upper pole and may be associated with a ureterocele (a cystic dilatation of the lower part of the affected ureter).

  • Megaureter refers to a ureter that exceeds the upper limit of normal size (>7 mm), and management is guided by the presence or absence of reflux or obstruction. Primary dilatation usually results from abnormal ureteric musculature, and affected ureters may show an adynamic segment of ureteric wall. Outflow obstruction with secondary ureteric dilatation may be seen in conditions such as posterior urethral valves or neuropathic bladder. Initial reflux is likely, but subsequent bladder wall thickening may result in ureteric obstruction. Surgical correction is generally advised for symptomatic patients.

5.4 Lower Urinary Tract Malformations

  • A variety of conditions give rise to bladder abnormalities or outflow obstruction which can have long-term consequences on both bladder and kidney function and thus quality of life. Kidney damage may be due to the effects of obstruction, but many cases are associated with abnormal kidney development. Bladder obstruction leads to bladder compensation with muscular hypertrophy. Further fibrosis leads to a non-compliant bladder with thickening and ‘stiffening’ of the bladder wall and may result in ureteric obstruction. In later stages the bladder may decompensate functioning as a floppy reservoir with little or no contractility. Regardless of bladder function, low-pressure storage and good drainage are essential. For some whose bladder has decompensated, intermittent self-catheterization may be necessary.

  • Posterior urethral valves (PUV) are the most common cause of congenital bladder outflow obstruction in male infants occurring in 1 in 5000–8000 pregnancies. The obstruction is caused by a membrane that extends across the posterior urethra. It is most commonly suspected antenatally with bilateral hydroureteronephrosis, a thick-walled bladder, and dilated posterior urethra (known as the keyhole sign) but may present after birth with a poor stream, straining to void, palpable bladder, enuresis, or urinary sepsis. Rare adult cases with end-stage kidney disease are still reported. Management involves immediate catheterization and confirmation of the diagnosis with a micturating cystogram (MCUG) – followed by valve resection. Many patients continue to have bladder dysfunction after surgical correction which necessitates clean intermittent self-catherization. Those with associated renal dysplasia and ongoing severe bladder dysfunction are at increased risk of developing CKD.

  • Prune belly syndrome predominantly occurs in males – diagnostic features include the partial aplasia or hypoplasia of the anterior abdominal wall muscles, gross dilatation of the bladder and ureters, and bilateral cryptorchidism. Men also characteristically have a dysplastic prostate and azoospermia. Although true outflow obstruction is sometimes present and should be corrected, the gross and irregular dilation of the urinary tract that is characteristic of this syndrome is primarily caused by replacement of smooth muscle with fibrous tissue leading to aperistaltic ureters. Urodynamics are often difficult to interpret because of gross VUR, but typically there is a low-pressure bladder. With late presentation, some patients have detrusor instability. Surgical intervention may be indicated to optimize urinary drainage and prevent recurrent UTIs. Approximately 50% of patients who survive infancy will develop CKD with the severity and timing dependent on the degree of associated renal dysplasia present.

  • Bladder exstrophy is a rare but significant congenital anomaly which occurs in 1 in 20,000–33,000 live births. The male to female ratio is 2:1 and offspring of affected individuals have an increased risk of 1 in 70 indicating some genetic predisposition. It is characterized by an open, ‘inside-out’ bladder which is fused with the lower abdominal wall and an open exposed dorsal urethra, requiring surgical reconstruction of the abdominal wall, bladder, bladder neck, and in a male infant, the penis. The reproductive, digestive, and urinary tracts as well as the abdominal wall and pelvic muscles are often affected. Occasionally, the more severe condition, cloacal exstrophy, is found; this is associated with other anomalies of the bowel or kidneys and may include neuropathic damage as a result of sacral agenesis or myelomeningocele. Only a third of patients empty their bladder via the urethra with the remainder requiring a urinary diversion (see ◘ Fig. 56.1). Long-term renal outcomes are generally good.

  • Neuropathic bladder dysfunction can occur in patients with spina bifida, especially when associated with myelomeningocele. Approximately 30–40% of children will develop some degree of CKD, usually associated with a lack of coordination between the detrusor and external sphincter. Detrusor overactivity causes high functional bladder pressures with uncontrolled contractions against a closed sphincter, resulting in upper tract damage. Low bladder pressures with incomplete bladder emptying and urinary sphincter incompetence can also result in urinary stasis and recurrent infections. Early initiation of clean intermittent self-catheterization and the use of anticholinergics or botulinum toxin type A for high pressure or hyperreflexic bladders can help to preserve renal function and promote continence.

  • Urofacial or Ochoa syndrome is an extremely rare autosomal recessive disease characterized by facial grimacing when attempting to smile and a neuropathic bladder. They are at risk of CKD.

Fig. 56.1
figure 1

MRI scan of the pelvis in a man with bladder exstrophy

Full size image

6 Diagnosis and Monitoring

By the time an adolescent with CAKUT is seen in adult services, the diagnosis has usually been made, any corrective surgery is completed, and it is assumed that the urinary tract is not obstructed. It is important however that this be reviewed periodically and any increase in the frequency or severity of urinary tract infections or sudden decline in renal function should prompt further investigation for the presence of stones, obstruction, or dysfunctional bladder emptying (◘ Box 56.4). Patients with dysfunctional bladder emptying will commonly carry out clean intermittent self-catheterization, and adherence to this should be confirmed. Routine monitoring of renal function, blood pressure, and proteinuria should also be carried out in line with CKD guidelines.

7 Treatment

Without careful bladder management progressive, kidney damage will be seen in the first 5 years of life in 30–40% of children. This can be dramatically reduced or delayed by ensuring the native or reconstructed bladder is compliant, has low pressure, and provides good drainage. Clean intermittent self-catheterization plays a central role and anticholinergic medication offers additional benefit by improving bladder capacity [13].

7.1 Ureterosigmoidostomy

Now rarely seen, this technique used until the 1970s, anastomosed the ureters directly onto the sigmoid colon, and was most commonly used in patients with bladder exstrophy. Progressive CKD, hyperchloraemic, hypokalaemic metabolic acidosis, kidney stones, infection, ureteral strictures, and increased risk for colonic carcinoma are important complications. Patients with ureterosigmoidostomy require annual flexible sigmoidoscopy.

7.2 Ileal Conduit (Urostomy)

The ureters are attached to an isolated segment of ileum and urine drains into a stoma bag. The ileal conduit is free flowing with rapid urinary transit and no reservoir (see ◘ Fig. 56.2). Metabolic complications are much less common, but hyperchloraemic metabolic acidosis can still occur as the bowel exchanges sodium and chloride for potassium and bicarbonate. Long-term complications of conduits include strictures, obstruction, calculi, vitamin B12 deficiency, and malignancy at the intestinal-ureteral anastomosis [14].

Fig. 56.2
figure 2

Loopogram to examine an ileal conduit

Full size image

7.3 Neobladder (Bladder Reconstruction)

Bowel is used to augment or completely replace the native bladder. A Mitrofanoff channel using appendix or small bowel may also be necessary to allow bladder drainage. This provides a continent, cutaneous channel for catheterization. Complications include infection, mucus production, kidney stones, and CKD. Lifelong follow-up is needed to detect medical or surgical complications. Excess mucus production can be treated with regular bladder washouts.

8 Complications

8.1 Urinary Tract Infections

Recurrent UTIs may be associated with urinary stasis, vesicoureteral reflux, stones, obstruction, or inadequate self-catheterization. An increase in the frequency or severity of UTIs should prompt investigation for stones or obstruction including CT KUB, renal ultrasound, and post-micturition residual volume. Patients with reconstructed bladders often have abnormal urinalysis and positive urine cultures and should be advised to increase fluid intake and the frequency of self-catheterization if they have any signs of cloudy or offensive urine. Only symptomatic infections should be treated with antibiotics.

8.2 Stones

Kidney stones may form in the presence of infected urine and are typically magnesium ammonium phosphate (struvite) or calcium phosphate [15]. In 90% of patients, the infecting organism is Proteus species. Stones (usually calcium phosphate) are common in cystoplasties and ileal conduits (5–30%) because of the alkaline environment. Upper tract stones must be suspected if UTIs recur or become more frequent; there is a sudden onset of severe pain and renal function suddenly deteriorates or there is an unexplained sterile pyuria.

8.3 Hypertension

Hypertension is common in the presence of scarred kidneys due to glomerular hyperfiltration and should be treated as per CKD guidelines. In patients with CKD secondary to obstruction, volume contraction may occur with subsequent normal or only mildly elevated blood pressure and diuretics should therefore be avoided.

8.4 Chronic Kidney Disease

The renal outcome of patients with CAKUT is similar whether there is primary renal dysplasia or abnormal bladder function. Predictive factors include GFR and degree of proteinuria. In young adults a GFR of less than 40mls/min/1.73m2 and proteinuria greater than 100 mg/mmol are poor prognostic indicators [16]. ACE inhibitors or angiotensin receptor blockers (ARB) are preferred for patients with proteinuria and progressive renal failure. Interestingly, a 2018 study of 3198 adolescents with a diagnosis of CAKUT but normal renal function and blood pressure who were followed up for 30 years reported an increased risk for ESRD (HR 5.19) [17], highlighting the importance of long-term follow-up for patients even with normal renal function as an adolescent.

8.5 Acidosis and Bone Disease

There is often a metabolic acidosis disproportionate to the degree of renal impairment. Metabolic acidosis was particularly common with ureterosigmoidostomy. It is our practice to give sufficient sodium bicarbonate to correct the plasma bicarbonate into the normal range. In addition to the typical bone disease of progressive CKD, acidosis contributes significantly to osteomalacia.

8.6 Tubular Dysfunction

Renal failure secondary to obstruction can cause significant tubular injury which may cause problems with urinary concentration, acidification, and sodium reabsorption. In this situation nocturia and polyuria are frequently reported, and a 24-hr urine volume diary should be completed to assess this objectively. Patients who are salt depleted typically present volume contracted and should be advised to increase their salt intake with close monitoring on blood pressure.

9 Transplantation

Many young people with CAKUT will have received a renal transplant in childhood and subsequently transition into an adult transplant clinic for continued follow-up. Transition to adult services is known to be associated with increased graft loss among adolescents [18], and a specialist young person’s service should be in place with support from a multidisciplinary team involving youth workers, clinical nurse specialists, and paediatric and adult nephrologists and urologists. Particular vigilance for recurrent urinary tract infections in patients with abnormal bladders is necessary. Any increase in frequency should prompt screening for stones in the graft or native kidneys and consideration of urodynamics. A significant post-micturition residual volume may require clean intermittent self-catheterization to ensure adequate bladder emptying.

Given the median age for reaching ESRD in patients with CAKUT is 31 years old [4], the majority of these patients will require assessment for transplantation within adult services and an algorithm to help guide pre-transplant assessment in patients with abnormal lower urinary tracts is given in ◘ Fig. 56.3. Thorough assessment of bladder function is key, and even patients with CAKUT and seemingly normal bladders should have a baseline postmicturition bladder ultrasound and urinary flow rate.

Fig. 56.3
figure 3

A suggested algorithm for pre-transplant assessment of a patient with CAKUT and abnormal lower urinary tract

Full size image

From our local experience, there was no difference in 10-year graft survival between patients with renal dysplasia and normal bladders (61%) compared to those with augmented bladders or urinary diversions (66%); however, longer-term follow-up did show an advantage in graft survival for patients with normal bladders [19].

Tips, Tricks, and Pitfalls

  1. 1.

    CAKUT are the most common cause of CKD in childhood and are probably under-diagnosed in young adults. A careful history and investigation will improve diagnosis.

  2. 2.

    A detailed family history is always needed as there is a strong genetic predisposition to many CAKUT phenotypes.

  3. 3.

    Proteinuria is a key prognostic indicator and probably reflects hyperfiltration injury. Treatment goals should be as for other causes of proteinuric CKD.

  4. 4.

    When investigating possible renal tract obstruction, start distally, i.e. urethra, and work back towards kidneys.

  5. 5.

    Lifelong follow-up is usually needed. Pay particular care to metabolic complications in patients with bladder reconstructions, i.e. acidosis, stone disease and bone mineral metabolism.

  6. 6.

    Abnormal or reconstructed bladders may be of large capacity which can lead to functional obstruction at high volumes. In general bladder volumes should be kept low, i.e. less than 400 ml. This can easily be assessed with 24 or 48 h recording of urine volumes together with fluid intake. Many patients will have been instructed to drink large volumes, and this childhood habit can be hard to break!

  7. 7.

    Patients with reconstructed bladders or urinary diversions will often have abnormal urinalysis and culture-positive MSU. Only treat for UTI if symptomatic.

Chapter Review Questions

  1. 1.

    Clinical manifestations of HNF1B-related disease include:

    1. (a)

      Renal cysts

    2. (b)

      Early-onset diabetes-mellitus

    3. (c)

      Neuropathic bladder

    4. (d)

      Hypomagnesaemia

    5. (e)

      All of the above

  2. 2.

    Which of the following statements is false with regards to prune belly syndrome?

    1. (a)

      It occurs exclusively in males.

    2. (b)

      Up to 50% will develop CKD depending on the degree of associated renal dysplasia and bladder dysfunction.

    3. (c)

      It is characterized by absent anterior abdominal wall muscles, gross dilatation of the bladder and ureters, and bilateral cryptorchidism.

    4. (d)

      It is usually associated with infertility.

  3. 3.

    UTIs in patients with augmented bladders may be associated with all of the following except:

    1. (a)

      Stones

    2. (b)

      A lack of symptoms

    3. (c)

      Poor bladder emptying

    4. (d)

      Mucus production

  4. 4.

    When assessing a patient with CAKUT for possible transplantation, the following are true except for:

    1. (a)

      It is essential to carry out a urinary flow rate and post-micturition bladder ultrasound in all patients.

    2. (b)

      Patients with small volume, non-compliant bladders should undergo bladder cycling +/− suprapubic catheterization.

    3. (c)

      Patients with post-void residual volumes of >100mls should be taught how to carry out clean intermittent self-catheterization.

    4. (d)

      Patients with ileal conduits require assessment with videocystometrogram (VCMG).

  5. 5.

    Complications seen in patients with urinary diversions include:

    1. (a)

      Hyperchloraemic metabolic acidosis

    2. (b)

      Stones

    3. (c)

      Malignancy

    4. (d)

      Vitamin B12 deficiency

    5. (e)

      All of the above

Answers

  1. 1.

    (a), (b), and (d). HNF1B-related disease is inherited in an autosomal dominant manner and has a variable phenotype which may include renal cysts, renal hypoplasia, single or duplex kidney, early-onset diabetes mellitus, pancreatic hypoplasia, abnormal liver function tests, hypomagnesaemia, early-onset gout, and genital tract malformations. It is not associated with a neuropathic bladder.

  2. 2.

    (a). Prune belly syndrome is seen predominantly in males; however, it can also rarely occur in females.

  3. 3.

    (b). Patients with urinary diversions and augmented bladders will often have an abnormal urinalysis and positive urine culture. Antibiotics should only be started in the presence of symptoms.

  4. 4.

    (d). Pre-transplant assessment of patients with ileal conduits requires a loopogram (contrast is injected into the conduit under fluoroscopy) to exclude obstruction or strictures and endoscopy to exclude malignancy at the intestinal-ureteral anastomosis.

  5. 5.

    (e). All the above can occur.

9 Conclusion

CAKUT encompasses a diverse range of structural malformations which together account for up to 50% of CKD and ESRD in children and places a significant health, educational, and economic burden on young people and their families. Patients may have had significant urological intervention as a child or have associated extra-renal anomalies requiring joined up and holistic care, particularly through the transition to adult services. Long-term follow-up for both urological and CKD complications is necessary, as even patients with normal renal function in adolescence remain at increased risk of developing ESRD.

9 Case Study 1

A 25-year-old man is referred to general nephrology clinic with hypertension and proteinuria following a recent diagnosis of type 2 diabetes mellitus for which he takes metformin. He was previously fit and well and is asymptomatic. On specific questioning he mentions that his mother also has type 2 diabetes which was diagnosed at a similar age and he has no other siblings as his mother unfortunately suffered multiple miscarriages. There is nothing significant to find on clinical examination except for an elevated blood pressure of 146/95. Blood tests show normal renal function with mildly elevated liver function tests, hypomagnesaemia, and a raised urate level. HbA1c is mildly elevated at 50 mmol/mol. Urine PCR is 50 mg/mmol and a renal ultrasound shows bilateral cystic dysplastic kidneys. He is diagnosed with CAKUT. Given his diabetes, renal cysts, and blood test abnormalities, a blood sample is sent for sequencing and dosage analysis of HNF1B, and a heterozygous pathogenic variant is reported. The results are explained to him, and he is counselled that any future offspring will have a 50% chance of inheriting the variant but that the clinical manifestations of HNF1B-related disease are highly variable. He continues to be followed up annually in the renal clinic for his CKD.

9 Case Study 2

A 22-year-old woman attends the nephrology clinic reporting increased frequency of UTIs. She was born with a cloacal malformation (the rectum, vagina, and urethra drain into a single common channel) requiring reconstructive surgery as a child, including bladder augmentation, and uses a Mitrofanoff stoma for intermittent self-catheterization. She has associated renal dysplasia and CKD stage 3b. An ultrasound showed no hydronephrosis, but CT KUB demonstrated stones in the neobladder for which she underwent cystoscopy and percutaneous lithotripsy. To prevent recurrent stones, she was advised to increase fluid intake to 2–3 L/day, perform regular bladder irrigation to aid mucus clearance, and increase self-catheterization to every 3–4 hours.