Haemolytic-uremic syndrome (HUS) is a clinical syndrome characterized by progressive renal failure that is associated with microangiopathic (nonimmune, Coombs-negative) haemolytic anaemia and thrombocytopenia. HUS is the most common cause of acute kidney injury in children. It predominantly occurs in infants and children after prodromal diarrhoea. In summer epidemics, the disease may be related to infectious causes.Bacterial infections may include the following:S dysenteriaeE ColiSalmonella typhiCampylobacter jejuniYersinia pseudotuberculosisNeisseria meningitidisS pneumoniaLegionella pneumophilaMycoplasma speciesRickettsial infections may include Rocky Mountain spotted fever and microtatobiotesViral infections may include the following:Human immunodeficiency virus (HIV)CoxsackievirusEchovirusInfluenza virusEpstein-Barr virusHerpes simplex virusFungal infections can include Aspergillus fumigatus.Vaccinations may include the following:Influenza triple-antigen vaccineTyphoid-paratyphoid A and B (TAB) vaccinePolio vaccinePregnancy-associated HUS occasionally develops as a complication of preeclampsia. Patients may progress to full-blown haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Postpartum HUS usually occurs within 3 months of delivery. The prognosis is poor, with a 50-60% mortality rate, and residual renal dysfunction and hypertension occur in most patients.

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.

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.

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.

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.

Henoch–Schönlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bleeding underneath the skin), often with joint pain and abdominal pain. It is an acute immunoglobulin A (IgA)–mediated disorder. The tetrad of purpura, arthritis, kidney inflammation, and abdominal pain is often observed.

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.

E. coli accounts for the majority of UTI’s in children. If this child responds well to treatment and has no recurrence of his symptoms, then no form of imaging is required, as per NICE advice for children aged 6 months to 3 years. Had the child been less than 6 months of age, then a USS at 6 weeks would be necessary.Other options:- Pseudomonas causes atypical UTI. This warrants ultrasonography within the acute illness phase as it may reflect an underlying pathology and DMSA at 4-6 months.- Recurrent UTI is defined as two or more episodes of pyelonephritis OR 1 pyelonephritis and one cystitis OR 3 or more cystitis. It requires USS at six weeks and DMSA at 4-6 months.- Septicaemia is a sign of an atypical UTI. This requires USS within the acute illness as it may reflect an underlying pathology and DMSA at 4-6 months.- Unwell 48hrs post antibiotics is a sign of an atypical UTI. This requires USS within the acute illness as may reflect underlying pathology and DMSA at 4-6 months.

Based on the presented clinical scenario, the most probable diagnosis for the patient would be testicular torsion.Rationale:The gubernaculum is the structure responsible for aiding the descent of the testicles from the abdomen into the scrotum. The processus vaginalis precedes the descent of the testes and then undergoes closure. Abnormalities such as the persistence of a patent processus vaginalis, known as bell clapper deformity, predispose to testicular torsion.Other options:- Varicocele: Nutcracker syndrome occurs where the left renal vein becomes compressed in between the superior mesenteric artery and the aorta. Since the left gonadal vein drains into the left renal vein, this results in a varicocele. – Epididymitis and mumps orchitis are differentials for acute testicular pain but are not due to a defect in the processus vaginalis. – An incarcerated inguinal hernia presents mainly with signs of bowel obstruction which are not mentioned in the clinical scenario.The descent of testes:- Until the end of foetal life, the testicles are located within the abdominal cavity. – They are initially located on the posterior abdominal wall on a level with the upper lumbar vertebrae (L2). – Attached to the inferior aspect of the testis is the gubernaculum testis which extends caudally to the inguinal region, through the canal and down to the superficial skin. – It is interesting to note that both the testis and the gubernaculum are extra-peritoneal.- As the foetus grows, the gubernaculum becomes progressively shorter. It carries the peritoneum of the anterior abdominal wall (the processus vaginalis). As the processus vaginalis descends the testis is guided by the gubernaculum down the posterior abdominal wall and the back of the processus vaginalis into the scrotum.- By the third month of foetal life the testes are located in the iliac fossae, by the seventh they lie at the level of the deep inguinal ring.Usually, the processus vaginalis closes after birth but may persist predisposing to indirect hernias. On the other hand, a partial closure may result in the development of cysts on the cord.

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.

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.

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

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.

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 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.

The most probable cause for the child’s presenting symptoms and the findings in ultrasound would be the presence of an abnormal posterior urethral valve. A posterior urethral valve is a developmental anomaly that usually affects male infants (incidence 1 in 8000) leading to obstructive uropathy. Diagnostic features include bladder wall hypertrophy, hydronephrosis and bladder diverticula.Note:Posterior urethral valves are the most common cause of infra-vesical outflow obstruction in males. They can be diagnosed on antenatal ultrasonography. Due to the necessity of the fetal bladder to develop high emptying pressures in utero secondary to this anomaly, the child may develop renal parenchymal damage. This leads to renal impairment noted in 70% of boys at the time of presentation. Management:The immediate treatment would be to place a bladder catheter to relieve the acutely retained urine. The definitive treatment of choice would be an endoscopic valvotomy with a cystoscopic and renal follow up.

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.

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.

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.

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.

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.

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.

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.

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

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.

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 child requires frequent BP evaluation every 15 to 30 minutes. Normalisation of his BP should be achieved in a 48h interval. An ophthalmology assessment is indicated to check for acute injury of the blood vessels in the eye due to the elevated blood pressure.

Hypospadias is an abnormality of anterior urethral and penile development. The urethral opening is located on the ventral aspect of the penis proximal to the tip of the glans penis, which, in this condition, is open. The urethral opening may be located as proximal as in the scrotum or perineum. The penis may also have associated ventral shortening and curvature, called chordee, with more proximal urethral defects.

Immunoglobulin G (IgG) glomerular immune deposits are seen more commonly in HSP compared to IgA nephropathy.The presentation of the child is highly suggestive of Henoch-Schönlein purpura (HSP). It is an IgA-mediated, autoimmune hypersensitivity vasculitis that targets the small vessels of the skin, GI tract, kidneys, and joints.It is most commonly seen in children aged 3 – 6years and is twice as common in boys than girls. Preceding viral URTI with low-grade pyrexia is common. The most common organism associated with HSP is, however, Group A streptococcal infection A.A purpuric rash is seen on the back of the legs and buttocks and can less frequently, affect the arms. Arthralgia is common (usually knees/ankles) in these patients. Abdominal pain and bloody diarrhoea may occur. And half of the children with HSP have renal involvement. Rarely, it can lead to end-stage renal failure.Treatment includes adequate hydration, occasionally steroids, and other immunosuppressants. The disease can recur in 1 in 3 children.

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, although other inheritance patterns exist. 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.