Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia.

This leads to the clinical features of dRTA:

- Normal anion gap metabolic acidosis/acidemia

- Hypokalemia

- Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate).

- Nephrocalcinosis (deposition of calcium in the substance of the kidney)

- Bone demineralisation (causing rickets in children and osteomalacia in adults)

The symptoms and sequelae of dRTA are variable and range from being completely asymptomatic, to loin pain and hematuria from kidney stones, to failure to thrive and severe rickets in childhood forms as well as possible renal failure and even death.

dRTA commonly leads to sodium loss and volume contraction, which causes a compensatory increase in blood levels of aldosterone. Aldosterone causes increased resorption of sodium and loss of potassium in the collecting duct of the kidney, so these increased aldosterone levels cause the hypokalemia which is a common symptom of dRTA.

An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications):

Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated cells of the medullary collecting duct of the distal nephron.

This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because renal excretion is the primary means of eliminating from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H while cannot be reclaimed by the cell, leading to acidemia (as builds up in the body) and hypokalemia (as cannot be reabsorbed by the alpha cell).

This leads to the clinical features of dRTA; In other words, the intercalated cells' apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types.

- Normal anion gap metabolic acidosis/acidemia

- Hypokalemia, Hypocalcemia, Hyperchloremia

- Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate).

- Nephrocalcinosis (deposition of calcium in the substance of the kidney)

- Bone demineralisation (causing rickets in children and osteomalacia in adults)

- Sjogren's syndrome

Distal renal tubular acidosis (dRTA) or Type 1 renal tubular acidosis (RTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3.

Proximal renal tubular acidosis (pRTA) or Type 2 Renal tubular acidosis (RTA) is a type of RTA caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalised dysfunction of the proximal tubular cells called Fanconi syndrome where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria.

Patients with type 2 RTA are also typically hypokalemic due to a combination of secondary hyperaldosteronism, and potassium urinary losses - though serum potassium levels may be falsely elevated because of acidosis. Administration of bicarbonate prior to potassium supplementation might lead to worsened hypokalemia, as potassium shifts intracellularly with alkanization.

The principal feature of Fanconi syndrome is bone demineralization (osteomalacia or rickets) due to phosphate and vitamin D wasting.

Familial disorders

- Cystinosis

- Galactosemia

- Glycogen storage disease (type I)

- Hereditary fructose intolerance

- Lowe syndrome

- Tyrosinemia

- Wilson's disease

Acquired disorders

- Amyloidosis

- Multiple myeloma

- Paroxysmal nocturnal hemoglobinuria

- Toxins, such as HAART, ifosfamide, lead, and cadmium

Hypouricemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 micromol/L (6 mg/dL) for women and 619 micromol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition.

Dent's disease often produces the following signs and symptoms:

- Extreme thirst combined with dehydration, which leads to frequent urination

- Nephrolithiasis (kidney stones)

- Hypercalciuria (high urine calcium - >300 mg/d or >4 mg/kg per d) with normal levels blood/serum calcium)

- Aminoaciduria (amino acids in urine)

- Phosphaturia (phosphate in urine)

- Glycosuria (glucose in urine)

- Kaliuresis (potassium in urine)

- Hyperuricosuria (excessive amounts of uric acid in the urine)

- Impaired urinary acidification

- Rickets

In a study of 25 patients with Dent's disease, 9 of 15 men, and one of 10 women suffered end-stage kidney disease by the age of 47.

A urinalysis will typically show a decreased urine sodium level, a high urine creatinine-to-serum creatinine ratio, a high urine urea-to-serum urea ratio, and concentrated urine (determined by osmolality and specific gravity). None of these is particularly useful in diagnosis.

In pre-renal and post-renal azotemias, elevation of the BUN exceeds that of the creatinine (i.e., BUN>12*creatinine). This is because BUN is readily absorbed while creatinine is not. In congestive heart failure (a cause of pre-renal azotemia) or any other condition that causes poor perfusion of kidneys, the sluggish flow of glomerular filtrate results in excessive absorption of BUN and elevation of its value in blood. Creatinine, however, is not absorbable and therefore does not rise significantly. Stasis of urine in post-renal azotemia has the same effect.

Though this condition is usually asymptomatic, if symptoms are present they are usually related to the causative process, (e.g. hypercalcemia). Some of the sympotoms that can happen are blood in the urine, fever and chills, nausea and vomiting, severe pain in the belly area, flanks of the back, groin, or testicles.

These include renal colic, polyuria and polydipsia:

- Renal colic is usually caused by pre-existing nephrolithiasis, as may occur in patients with chronic hypercalciuria. Less commonly, it can result from calcified bodies moving into the calyceal system.

- Nocturia, polyuria, and polydipsia from reduced urinary concentrating capacity (i.e. nephrogenic diabetes insipidus) as can be seen in hypercalcemia, medullary nephrocalcinosis of any cause, or in children with Bartter syndrome in whom essential tubular salt reabsorption is compromised.

There are several causes of nephrocalcinosis that are typically acute and present only with renal failure. These include tumor lysis syndrome, acute phosphate nephropathy, and occasional cases of enteric hyperoxaluria.

Azotemia has three classifications, depending on its causative origin. A BUN/Cr > 20 tends to herald prerenal azotemia (commonly secondary to dehydration but also any other reason perfusion to kidneys is decreased). The BUN-to-creatinine ratio (BUN:Cr) is a useful measure in determining the type of azotemia. A normal BUN:Cr is equal to 15.

Hypouricemia is not a medical condition itself (i.e., it is benign), but it is a useful medical sign. Usually hypouricemia is due to drugs and toxic agents, sometimes it is due to diet or genetics, and rarely it is due to an underlying medical condition. When one of these causal medical conditions is present, hypouricemia is a common sign.

The differential diagnosis of normal anion gap acidosis is relatively short (when compared to the differential diagnosis of "acidosis"):

- Hyperalimentation

- Acetazolamide and other carbonic anhydrase inhibitors

- Renal tubular acidosis

- Diarrhea: due to a loss of bicarbonate. This is compensated by an increase in chloride concentration, thus leading to a normal anion gap, or hyperchloremic, metabolic acidosis. The pathophysiology of increased chloride concentration is the following: fluid secreted into the gut lumen contains higher amounts of Na than Cl; large losses of these fluids, particularly if volume is replaced with fluids containing equal amounts of Na and Cl, results in a decrease in the plasma Na concentration relative to the Clconcentration. This scenario can be avoided if formulations such as lactated Ringer’s solution are used instead of normal saline to replace GI losses.

- Ureteroenteric fistula - an abnormal connection (fistula) between a ureter and the gastrointestinal tract

- Pancreaticoduodenal fistula - an abnormal connection between the pancreas and duodenum

- Spironolactone

As opposed to high anion gap acidosis (which involves increased organic acid production), normal anion gap acidosis involves either increased production of chloride (hyperchloremic acidosis) or increased excretion of bicarbonate.

Nephrocalcinosis Is connected with conditions that cause hypercalcemia, hyperphosphatemia, and the increased excretion of calcium, phosphate, and/or oxalate in the urine. A high urine pH can lead to Nephrocalcinosis. In conjustion with Nephrocalcinosis, hypercalcemia and hypercalciuria the following can occur:

- Primary hyperparathyroidism: Nephrocalcinosis is one of the most common symptoms of primary hyperparathyroidism.

- Sarcoidosis: Nephrocalcinosis is one of the most common symptoms.

- Vitamin D therapy: This can cause nephrocalcinosis because of Vitamin D therapy becauseit increase the absorption of ingested calcium and bone resorption, resulting in hypercalcemia and hypercalciuria.

In general, the cause of a hyperchloremic metabolic acidosis is a "loss of base", either a gastrointestinal loss or a renal loss.

- Gastrointestinal loss of bicarbonate ()

- Severe diarrhea (vomiting will tend to cause hypochloraemic alkalosis)

- Pancreatic fistula with loss of bicarbonate rich pancreatic fluid

- Nasojejunal tube losses in the context of small bowel obstruction and loss of alkaline proximal small bowel secretions

- Chronic laxative abuse

- Renal causes

- Proximal renal tubular acidosis with failure of resorption

- Distal renal tubular acidosis with failure of secretion

- Long-term use of a carbonic anhydrase inhibitor such as acetazolamide

- Other causes

- Ingestion of ammonium chloride, hydrochloric acid, or other acidifying salts

- The treatment and recovery phases of diabetic ketoacidosis

- Volume resuscitation with 0.9% normal saline provides a chloride load, so that infusing more than 3-4L can cause acidosis

- Hyperalimentation ("i.e.", total parenteral nutrition)

Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration (see anion gap for a fuller explanation). Although plasma anion gap is normal, this condition is often associated with an "increased" urine anion gap, due to the kidney's inability to secrete ammonia.

Inborn errors of renal tubular transport are metabolic disorders which lead to impairment in the ability of solutes, such as salts or amino acids, to be transported across the brush border of the renal tubule. This results in disruptions of renal reabsorption.

Examples of these disorders include Iminoglycinuria, renal tubular acidosis and Gitelman syndrome.

Classical signs of uremia are: progressive weakness and easy fatigue, loss of appetite due to nausea and vomiting, muscle atrophy, tremors, abnormal mental function, frequent shallow respiration and metabolic acidosis. Without intervention via dialysis or kidney transplant, uremia due to renal failure will progress and cause stupor, coma and death. Because uremia is mostly a consequence of kidney failure, its signs and symptoms often occur concomitantly with other signs and symptoms of kidney failure. Below is a table showing more of the principal signs and symptoms of uremia.

Glomerular filtration rate (GFR) measures the amount of plasma being filtered through the kidneys. As the GFR decreases, the prognosis worsens. Some of the effects can be reversed with dialysis. See below for a chart on GFR rates and their effects.

In renal physiology, normal anion gap acidosis, and less precisely non-anion gap acidosis, is an acidosis that is "not" accompanied by an abnormally increased anion gap.

The most common cause of normal anion gap acidosis is diarrhea with a renal tubular acidosis being a distant second.

The clinical features of proximal renal tubular acidosis are:

- Polyuria, polydipsia and dehydration

- Hypophosphatemic rickets (in children) and osteomalacia (in adults)

- Growth failure

- Acidosis

- Hypokalemia

- Hyperchloremia

Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:

- Hypophosphatemia/hyperphosphaturia

- Glycosuria

- Proteinuria/aminoaciduria

- Hyperuricosuria

People on dialysis acquire what is known as "residual syndrome". Residual syndrome is a non-life-threatening disease which is displayed as toxic effects causing many of the same signs and symptoms that uremia displays. There are several hypotheses why residual syndrome is present. They are: (1) the accumulation of large molecular weight solutes that are poorly dialyzed (e.g. β-Microglobulin), (2) the accumulation of protein-bound small molecular weight solutes that are poorly dialyzed (e.g. "p"-cresyl sulfate and indoxyl sulfate), (3) accumulation of dialyzable solutes that are incompletely removed (e.g. sequestered solutes like phosphate in cells or insufficient elimination of other more toxic solutes), (4) indirect phenomena such as carbamylation of proteins, tissue calcification, or a toxic effect of hormone imbalance (e.g. Parathyroid hormone) and (5) the toxic effect by dialysis itself (e.g. removal of unknown important vitamins or minerals). Dialysis increases life span but patients may have more limited function. They gain physical limitations which include impairment of balance, walking speed and sensory functions. They also retain cognitive impairment such as impairment in attention, memory and performance of higher-order tasks. Patients have been maintained longer than three decades on dialysis, but unfortunately average mortality rates and hospitalizations are high. Also patient rehabilitation and quality of life is poor.

The symptoms of an elevated potassium level are nonspecific, and generally include malaise, palpitations, and muscle weakness. Hyperventilation may indicate a compensatory response to metabolic acidosis, which is one of the possible causes of hyperkalemia. Often, however, the problem is detected during screening blood tests for a medical disorder, or after hospitalization for complications such as cardiac arrhythmia or sudden cardiac death. High levels of potassium (> 5.5 mmol/L) have been associated with cardiovascular events.

Physicians taking a medical history may focus on kidney disease, medication use (e.g. potassium-sparing diuretics), which are common causes.

In terms of the signs/symptoms of medullary cystic kidney disease, the disease is not easy to diagnose and is uncommon. In this condition, loss of kidney function occurs slowly over time, however the following signs/symptoms could be observed in an affected individual:

Some individuals with this disease develop gout, which is a condition in which patients develop severe pain and swelling in the big toe or another joint such as the knee. If untreated, it becomes chronic and affects the joints most of the time, instead of intermittently.

The main causes of hypokalemic acidosis are systemic disorders that can be divided into:

- Carbonic anhydrase inhibitors such as acetazolamide

- Dialysis, in the post-treatment

- Diarrhea

- Renal tubular acidosis

- Treated DKA with insulin therapy

- VIPoma

Symptoms are not specific, and diagnosis can be difficult unless the patient presents with clear indications for arterial blood gas sampling. Symptoms may include chest pain, palpitations, headache, altered mental status such as

severe anxiety due to hypoxia, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite and weight gain, muscle weakness, bone pain, and joint pain. Those in metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis. Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in some degree of compensation. Overcompensation via respiratory alkalosis to form an alkalemia does not occur.

Extreme acidemia leads to neurological and cardiac complications:

- Neurological: lethargy, stupor, coma, seizures

- Cardiac: arrhythmias (ventricular tachycardia) and decreased response to epinephrine, both leading to hypotension

Physical examination occasionally reveals signs of disease, but is otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol poisoning, and retinal edema can be a sign of methanol intoxication. Longstanding chronic metabolic acidosis leads to osteoporosis and can cause fractures.