Nephrogenic Diabetes Insipidus is an acquired or hereditary condition that affects the water balance. It presents with polyuria and polydipsia, leading commonly to dehydration.

Renal scaring resulting from urinary tract infections can best be determined using Dimercaptosuccinic acid (DMSA) scintigraphy. The scan utilises technetium-99 mixed with the DMSA which is injected into the bloodstream. The radiological dye is taken up by the kidney where it binds to the proximal convoluted tubules. It therefore detects the size, shape and position of the kidney and any scars but is not as useful in assessing dynamic renal excretion. Ultrasound scans are better suited to assess hydronephrosis and dilated ureters. MAG3 scans and MCUG are able to determine the function of kidneys and detect obstructions such as posterior urethral valves and reflux.

The patient shows features of neurofibromatosis. The most likely cause for hypertension in this patient would be renal artery stenosis.

Note:
Neurofibromatosis is an inherited autosomal dominant disorder which could have affected this girl’s father, and she appears to have the classic skin lesions.
A renal bruit might be heard in these patients.
Polycystic kidney disease can occur in association with tuberous sclerosis, which also has skin lesions associated (different from those described in this patient).
Most causes of hypertension in childhood have underlying renal causes, and a renal ultrasound with doppler is the first-line investigation of choice. Even if this is normal, further imaging would be indicated here, for example, isotope renal scans and angiography.

Polyuria is defined as a total increase in the urine output or > 2L/m2 of daily urine produced in children. Polyuria can be a symptom of a vast number of medical conditions. The commonest and most important disease having polyuria as the main symptom is diabetes mellitus. Nephrogenic and central diabetes insipidus also results in polyuria along with polydipsia. Other conditions that lead to an increase in the urine output are renal failure, acute tubular necrosis, and exposure to high altitude. Hyperkalaemia does not result in polyuria; rather hypokalaemia can be an associated finding with polyuria in the case of diuretic abuse.

Coverings of the spermatic cord:
Spermatic cord is covered by three concentric layers of fasciae, derived from the layers the of anterior abdominal wall. Developmentally, each covering is acquired as the processus vaginalis descends into the scrotum through the layers of the abdominal wall. The layers are:

External spermatic fascia: It is derived from the external oblique muscle. It attaches to the margins of superficial inguinal ring.
Cremasteric fascia: It is derived from the internal oblique muscle. It covers the cremaster muscle.
Internal spermatic fascia: It is derived from the fascia transversalis (fascia covering the transversus abdominis muscle). It is attached to the margins of the deep inguinal ring.

Allergy: A history of a prior allergic-like reaction to contrast media is associated with an up to a 5-fold increase in the likelihood of experiencing a subsequent reaction. Also, any patient with a predilection to allergic reactions may predispose them to a reaction after the administration of contrast media. Given the increased risk of severe life-threatening anaphylaxis related to the administration of contrast media in the setting of the history of atopy, the risk versus benefits should be discussed before following through with the procedure. A premedication regimen may be used to reduce the risk of anaphylaxis.

Asthma: A history of asthma may be indicative of a higher likelihood of developing a contrast reaction.

Cardiac status: Attention must be turned to patients with significant cardiac disease (congestive heart failure, aortic stenosis, severe cardiomyopathy, and/or pulmonary hypertension), as higher volumes and osmolality of contrast material may result in an increased risk for a contrast reaction.

Renal insufficiency: Contrast nephrotoxicity is defined as the rapid deterioration of renal function after the administration of contrast media when no other aetiology can be determined from the clinical records. The major predisposing risk factors include pre-existing renal insufficiency (defined as serum creatinine level >1.5 mg/dL) and diabetes. Other risk factors include dehydration, cardiovascular disease, the use of diuretics, advanced age (>70 years old), hypertension, and hyperuricemia. Obtaining multiple contrast-enhanced studies within 24 hours is also thought to increase the risk for contrast-induced nephrotoxicity.

Miscellaneous: Relative contraindications to the use of high osmolality iodinated contrast media (HOCM) in patients with pheochromocytoma, sickle cell disease, and multiple myeloma have been reported. Although the administration of low osmolality or iso-osmotic contrast media may be beneficial in patients with pheochromocytoma and sickle cell disease, little evidence suggests that these agents mitigate the risks associated with multiple myeloma.

The most common physiological factors that influence renin secretion include renal perfusion pressure, renal sympathetic nerve activity, and tubular sodium chloride load.
The perfusion pressure in the renal artery is the most profound parameter to influence renin secretion; when the renal perfusion pressure falls (i.e. hypovolaemia), renin secretion rises, and vice versa.

Using a Doppler device, you can estimate systolic BP even when the pulse is inaudible. Handheld and portable, the device uses ultrasound waves to detect the velocity of arterial blood flow. Helpful for patients with traumatic injuries or shock, the Doppler technique is also useful for children and patients whose BP is hard to hear because of oedema, obesity, vasoconstriction, or low cardiac output.

Minimal change glomerulonephritis presents with mild or benign urinalysis findings. However, proteinuria together with the presence of oval fat bodies are typical.
Minimal change glomerulonephritis (nephropathy) accounts for most cases of childhood nephrotic syndrome and 20-25% of adult nephrotic syndrome.

Diffuse proliferative glomerulonephritis is a term used to describe a distinct histologic form of glomerulonephritis common to various types of systemic inflammatory diseases, including autoimmune disorders (e.g., systemic lupus erythematosus [SLE]), vasculitis syndromes (e.g., granulomatosis with polyangiitis), and infectious processes. In DPGN, more than 50% of the glomeruli (diffuse) show an increase in mesangial, epithelial, endothelial (proliferative), and inflammatory cells (i.e., glomerulonephritis).

Haemolytic uremic syndrome belongs to a heterogeneous group of disorders characterized by a triad of thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. It is one of the most common causes of renal injury in children. The clinical findings are due to thrombotic microangiopathy, which leads to arterioles and capillary wall thickening along with endothelial swelling and detachment. The significant laboratory findings include increased white cell count, raised serum urea and creatinine, increased serum LDH, decreased platelet count, haematuria, and proteinuria.

Fanconi tubular syndrome is characterised by malabsorption of various electrolytes and substances commonly absorbed by the proximal tubule. Hypokalaemia, hypophosphatemia, and hyperchloremic metabolic acidosis is usually present. Also, urinalysis reveals an increased fractional excretion of glucose.

The child has nephrotic syndrome which is most commonly caused by minimal change nephropathy in this age group. The condition presents with fusion of foot processes of the glomerular epithelial cells under the microscope.

The most probable diagnosis for this patient would be a duplex kidney with an ectopic ureter inserting below the bladder neck.

Rationale:
The Weigert-Myer law states that the upper moiety ureter inserts inferior and medial to the lower moiety ureter.

Other options:
– Horseshoe kidney would display as a single pelvic kidney on an ultrasound scan.
– Ureterocele would be a cystic lesion within the bladder or may prolapse at birth.
– Continence should not be affected by polycystic kidney disease.
– The overactive bladder would cause frequency and urgency, neither of which is mentioned in the history.

Vesicoureteric reflex (VUR) is described as the retrograde flow of urine from the bladder into the ureter due to an incompetent uterovesical junction. In primary VUR the lower urinary tract functions normally, while secondary VUR is associated with a poorly functioning lower urinary tract. The incidence of VUR is highest in new-born girls. They can present with hydronephrosis, or urinary tract infections.

Minimal change nephrotic syndrome leads to the loss of anti-thrombin III which protects the body from forming venous emboli. It may be triggered by virus, immunisations, medication, non-Hodgkin lymphoma, or leukaemia
Characterised by oedema, proteinuria, hypoalbuminemia, and hypercholesterolemia.

The child has a history of pharyngitis followed 10 days later by signs of glomerulonephritis. In this particular case, it is most probably a post-streptococcus glomerulonephritis which accounts for 80% of paediatric cases of glomerulonephritis.

In nephrotic syndrome, one of the main pathological processes is the excretion of protein by the kidneys. The resultant signs including; low serum albumin, oedema and hypovolemia all occur as a result of fluid escaping into the extracellular space due to a low oncotic pressure. While an albumin infusion may help to increase oncotic pressure, its indications specifically include hypovolemia, which is assessed by a capillary refill time more than 5 seconds, an elevated haematocrit, or severe symptomatic oedema, such as scrotal oedema. Hypertension not an indication for an infusion, and most patients needing an albumin infusion have oliguria.

Distal renal tubular acidosis (dRTA) is characterised by a decreased hydrogen ion excretion from the alpha intercalated cells of the collecting duct of the distal nephron. The resultant acidosis causes calcium and phosphates to be released from bones to buffer the acidosis causing hypercalciuria. This precipitates calcium compounds in the kidney, predisposing it to renal stone formation. On the other hand, proximal renal tubular acidosis is characterised by an impairment in bicarbonate resorption. Both types lead to metabolic acidosis and electrolyte imbalances including potassium depletion. Children often present with failure to thrive. One way to differentiate between the two conditions is with an acid challenge test. In proximal RTA (type 2) administering an ammonium chloride load will decrease the urinary pH whereas in distal disease (type 1), the urine pH will not decrease below 5.3.

The mesonephric duct is one of the paired embryogenic tubules that drain the primitive kidney (mesonephros) to the cloaca. It also gives off a lateral branch forming the ureteric bud. In both the male and the female the Wolffian duct develops into the trigone of the urinary bladder.
When the ducts are exposed to testosterone during embryogenesis, male sexual differentiation occurs: the mesonephric duct develops into the rete testis, the ejaculatory ducts, the epididymis, the ductus deferens and the seminal vesicles.

The most common manifestation of Wilms tumour is an asymptomatic abdominal mass; an abdominal mass occurs in 80% of children at presentation. Abdominal pain or haematuria occurs in 25%. Urinary tract infection and varicocele are less common findings than these. Hypertension, gross haematuria, and fever are observed in 5-30% of patients. A few patients with haemorrhage into their tumour may present with hypotension, anaemia, and fever. Rarely, patients with advanced disease may present with respiratory symptoms related to lung metastases.

Prepubertal atrophic vaginitis is due to a lack of vaginal oestrogen. The pathophysiology behind prepubertal atrophic vaginitis:
1.The proximity of the vagina to the anus
2.Lack of oestrogen – leads to thinning of the vaginal mucosa
3.Lack of pubic hair to protect the area
4.Lack of labial fat pads

Fanconi syndrome is a rare disorder characterized by defective proximal renal tubular reabsorption, which leads to excessive excretion of potassium, phosphate, uric acid, bicarbonates, glucose, and certain amino acids in the urine. Loss of potassium in the urine leads to hypokalaemia, while the loss of phosphate may lead to hypophosphatemic rickets. The overall impact is the failure to thrive and growth retardation.

The presenting features with the positive pregnancy test are highly suggestive of gestational diabetes mellitus.

Diabetes Insipidus:
It is much less common than gestational diabetes mellitus. It is characterised by the inability to concentrate urine, with marked thirst.

Presenting symptoms include polydipsia (>3L daily), polyuria, nocturia, nocturnal enuresis.
Physical examination may reveal features of dehydration and an enlarged bladder.
Investigations include biochemical analysis for electrolytes, urine and plasma osmolality, fluid deprivation test, and cranial MRI.

The main differential diagnosis is for diabetes insipidus is psychogenic polydipsia.

There are three broad categories of diabetes insipidus (DI):
– Central (cranial) DI:
It is the most common form of diabetes insipidus.
It occurs due to decreased secretion of ADH. It usually occurs due to hypothalamic disease and may show response to low-dose desmopressin.
– Peripheral (nephrogenic) DI:
It is characterised by the resistance of the kidney to ADH.
It usually does not respond to low-dose desmopressin.
– Gestational DI:
It is rare and is mostly seen in teenage pregnancy.
It usually presents in the third trimester and often resolves 4-6 weeks post-partum.

Constipation is often associated with nocturnal enuresis in children. The palpable mass is the impacted stool. The decreased appetite is common in those with constipation.

Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.
Alport syndrome can have different inheritance patterns. About 80 percent of cases are caused by mutations in type IV collagen genes (COL4A5) and are inherited in an X-linked autosomal recessive pattern.
Alport syndrome has autosomal dominant inheritance in about 5 percent of cases.
People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (haematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD).
People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue at the back of the eye (retina). These eye abnormalities seldom lead to vision loss.
Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females.

The cells in the testes that secrete testosterone are the Leydig cells.

Other cells in testes include:
– Spermatogonia: These are undifferentiated male germ cells which undergo spermatogenesis in the seminiferous tubules of the testes.
– Sertoli cells: They are a part of the seminiferous tubule of the testes, cells are activated by FSH and nourish developing sperm cells.
– Myoid: They are squamous contractile cells which generate peristaltic waves, they surround the basement membrane of testes.
– Fibroblasts: Cells which synthesise collagen and the extracellular matrix.

Membranoproliferative glomerulonephritis primarily affects children and young adults, with patients presenting with nephrotic or nephritic syndrome or with asymptomatic renal disease. There are 3 types defined by pathologic features. All three types are associated with hypocomplementemia, but they manifest somewhat different mechanisms of complement activation. This type of glomerulonephritis often progresses slowly to end-stage renal disease, and it tends to recur after renal transplantation, especially type II.

The most probable diagnosis for this patient is bilateral retractile testes. This a normal phenomenon in some pre-pubertal boys.

Rationale:
Testicular descent can continue until about 3-months of age. The pre-pubertal testis is small enough that with activation of the cremasteric reflex, they can enter the inguinal canal.
This in itself is a normal finding providing the testis can be brought into the scrotum without tension and does not require surgical correction. With time the testis will lie within the scrotum.

Orchidopexy for true undescended testis can be performed from 6-months of age. It is also warranted if the testes remain undescended or intra-abdominally leading to infertility.

Other options:
– An ascending testis is one, typically, following hernia or orchidopexy surgery that was in the testis but with time is within the inguinal canal and cannot be brought into the scrotum. Orchidopexy is required for this.
– No surgery is required as when the testis enlarges with puberty it will remain within the scrotum.
– The testes can be brought into the scrotum. Therefore they are not undescended.
– The testes are retractile not ascending; ascending testis cannot be brought into the scrotum and would require orchidopexy.

Proteinuria refers to an increased amount of protein excretion in urine, which should be greater than 100mg/m2 per day on a single spot urine collection. The limit is even more relaxed for infants and neonates. Proteinuria is a prominent manifestation of cystinosis, acute tubular necrosis, Fanconi syndrome, and celiac disease. Landau-Kleffner syndrome is a rare childhood convulsive disorder, associated with acquired aphasia and auditory verbal agnosia.

ADH primarily acts on the collecting ducts.

Other options:
– The juxtaglomerular apparatus is the site of renin production.
– The proximal tubule conducts isosmotic reabsorption of about 60% of sodium chloride and volume. Most of the glucose, amino acids, potassium and phosphate are absorbed here.
– The loop of Henle is the site of 25% of sodium reabsorption. Active Chloride transport provides the basis for the counter current multiplier aiding urinary concentration.
– The distal convoluted tubule is impermeable to water and acts via active sodium chloride absorption to dilute urine.

Hyperkalaemia is not to evaluate or detect AKI but rather the result of it. If one of the rest of the options is present, then AKI would be suspected.

Vesicoureteral reflux is a common disorder in children but can result in kidney scarring following acute pyelonephritis. The gold standard diagnostic test to detect renal scars in children is 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy

The child most likely has nephritic syndrome which is characterised by a reduced renal function, proteinuria of non-nephrotic range, haematuria, erythrocyte casts, and oedema.

Polyarteritis nodosa usually occurs in middle-aged men but can also be seen in young children. It is accompanied by severe systemic manifestations such as fever, malaise, weight loss and myalgia.

Renal cell carcinoma usually presents around 55 years with the classic triad of haematuria, loin pain and a unilateral mass in the flank.

Polycystic kidney disease usually presents in adult life with acute loin pain and palpation of masses in the flanks.

Von Hippel-Lindau syndrome is a genetic disorder inherited in autosomal dominant fashion. It is caused by the mutations of the VHL gene located on chromosome 3. The syndrome is characterized by the creation of multiple benign and malignant tumours involving various bodily systems along with the formation of numerous visceral cysts, including the renal and epididymal cysts.
Down’s syndrome is associated with renal cysts, but it does not follow the autosomal dominant mode of inheritance, rather it is caused by non-disjunction of chromosome 21 during meiosis.
Exomphalos is a defect of the medial abdominal wall leading to abnormal protrusion of abdominal viscera through it. It is not associated with renal cysts.
Turner’s syndrome may be associated with renal cysts formation, but it is not transmitted in an autosomal dominant fashion.
Polycystic kidney disease of childhood follows an autosomal recessive pattern of transmission.

Distal renal tubular acidosis (dRTA) is characterised by a decreased hydrogen ion excretion from the alpha intercalated cells of the collecting duct of the distal nephron. The resultant acidosis causes Ca and phosphates to be released from bones to buffer the acidosis causing hypercalciuria, thus precipitating calcium compounds in the kidney. Other consequences of the dRTA in children include rickets, hypokalaemia, and polyuria. While dRTA can occur as a result of various pathologies including autoimmune disease, proximal renal tubular acidosis often presents as part of Fanconi’s syndrome. One way to differentiate between the two conditions is with an acid challenge test. In proximal RTA offering the child an acid load will decrease the urinary ph whereas in distal disease the pH will be unaffected due to impairment in hydrogen ion secretion.

Tuberous sclerosis presents with the growth of numerous noncancerous (benign) tumours in many parts of the body. They may appear in the brain, kidneys, skin or various other organs.

Progressive vomiting due to pyloric stenosis leads to hypochloraemic, hypokalaemic, metabolic alkalosis.

Among the given options, the most likely cause for the patient’s presenting symptoms is acute interstitial nephritis secondary to anti-tubercular therapy (ATT)
Drug-induced acute interstitial nephritis can occur following treatment with beta-lactams, sulphonamides, rifampicin, ethambutol, and erythromycin. They can cause an acute allergic reaction with the infiltration of immune cells.
Acute interstitial nephritis is said to be the most common renal complication in patients undergoing anti-TB treatment. Rifampicin is the most implicated drug, although ethambutol can also be a cause. The pathogenesis involves an immune-complex mediated acute allergic response, which leads to their deposition on renal vessels, the glomerular endothelium, and the interstitial area.

Other options:
Isoniazid does not affect the kidneys.
Pulmonary-renal syndrome is a feature of Goodpasture’s syndrome. It is characterized by renal failure and lung haemorrhage. Severe cardiac or renal failure ensues and is complicated by pulmonary oedema, systemic lupus erythematosus, Henoch-Schonlein purpura, and cryoglobulinemia.

Gitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.

The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence. Common features of this condition include painful muscle spasms (tetany), muscle weakness or cramping, dizziness, and salt craving. Also common is a tingling or prickly sensation in the skin (paraesthesia), most often affecting the face. Some individuals with Gitelman syndrome experience excessive tiredness (fatigue), low blood pressure, and a painful joint condition called chondrocalcinosis. Studies suggest that Gitelman syndrome may also increase the risk of a potentially dangerous abnormal heart rhythm called ventricular arrhythmia.